Instructions for medical use of the medicinal product
VIZARSIN®
Trade Name
Vizarsin®
International Nonproprietary Name
Sildenafil
Dosage form
Film-coated tablets, 25 mg, 50 mg, and 100 mg
Composition
One tablet contains
active ingredient – sildenafil (as sildenafil citrate) 25mg, 50 mg or 100 mg,
excipients: microcrystalline cellulose (Avicel pH 101), calcium hydrogen phosphate anhydrous, sodiumcroscarmellose, hypromellose (5 mPas), microcrystalline cellulose (AvicelPH 102), magnesium stearate,
Shell composition: hypromellose, lactose monohydrate, titanadioxide E171, triacetin.
Description
Oval, biconvex film-coated tablets, white or nearly white, labeled 25 on one side (for 25 mg dosage).
Oval, biconvex film-coated, white or nearly white film-coated tablets labeled 50 on one side (for 50 mg dosage).
Oval, biconvex film-coated tablets, white or nearly white, marked 100 on one side (for a dosage of 100 mg).
Pharmacotherapeutic group
Drugs for the treatment of erectile dysfunction disorders.
PBX code G04B E03
Pharmacological properties
Pharmacokinetics
Sildenafil is rapidly absorbed. Maximum plasma concentrations when ingested on an empty stomach are reached within 30 to 120 minutes (median 60 minutes). Absolute bioavailability averages about 40% (25-63%). After ingestion, the area under the concentration-time curve (AUC) and the maximum concentration (Cmax) of sildenafil increase in a dose-proportional manner within the recommended dose range (25-100 mg).
When sildenafil is taken with food, its absorption rate decreases, the time to reach maximum concentration (Tmax) increases by an average of 60 minutes, and Cmax decreases by an average of 29%.
The volume of distribution (Vd) of sildenafil in the equilibrium state averages 105 L, which means that it penetrates into tissues. After a single oral dose of 100 mg, the mean maximum total concentration of sildenafil is approximately 440 ng/mL (CV40%). Since sildenafil (and its major circulating Ndesmethyl metabolite) is 96% bound to plasma proteins, the mean plasma concentrations of the free fraction of sildenafil are 18 ng/mL (38 nM). Protein binding is independent of the total
concentration of the drug.
Sildenafil is metabolized primarily in the liver by the cytochrome P450 microsomal isoenzymes: CYP3A4 (main pathway) and CYP2C9 (accessory pathway). The major circulating active metabolite is formed by N-demethylation of sildenafil. This metabolite has a phosphodiesterase selectivity profile similar to that of sildenafil, and its activity against PDE5 is approximately 50% of that of the parent substance. The plasma concentration of the metabolite is about 40% of that of sildenafil. The N-demethylated metabolite undergoes further metabolism; Its terminal half-life is about 4 hours.
The total clearance of sildenafil from the body is 41 L/hr and the terminal half-life is 3-5 hours. Following oral or intravenous administration, sildenafil is excreted as metabolites, mainly in the faeces (approximately 80% of the dose) and to a lesser extent by urine (approximately 13% of the dose).
Pharmacokinetics in Special Patient Populations
Older:
In elderly patients (65 years of age and older), clearancessildenafil is reduced and plasma concentrations of sildenafil and its active N-desmethyl metabolite are approximately 90% higher. Due to age-related differences in plasma protein binding, the corresponding increase in plasma concentrations of sildenafil is 40%.
Renal impairment:
In patients with severely impaired renal function (creatinine clearance <30 mLmin), sildenafil clearance decreases, and mean AUC and cmax increase by 100% 88%, respectively. In addition, the values of the ndesmethyl metabolite are also 79% 200% respectively.
Pharmacodynamics
Vizarsine® is intended for oral therapy of erectile dysfunction. In natural conditions, i.e. in the presence of sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis.
The physiological process underlying penile erection involves the release of nitric oxide into the cavernous body under the influence of sexual stimuli. Nitric oxide activates the enzyme guanylate cyclase and increases cyclic guanosine monophosphate (cGMP), which relaxes the smooth muscle cells of the corpus cavernosa and promotes its filling with blood.
Vizarsin® is a potent and selective inhibitor of cycloguanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosa, where PDE5 is responsible for the breakdown of cGMP. Vizarsin® has a peripheral effect on erections.
Vizarsin® does not have a direct relaxing effect on the isolated human cavernous body, but enhances the relaxing effect of NO in this tissue. When the NO/cGMP bond is activated, which occurs under the influence of sexual stimuli, suppression of PDE5 by sildenafil leads to an increase in cGMP in the corpus cavernosa. Thus, sexual stimulation is necessary for the development of the desired pharmacological action of sildenafil.
In vitro studies have shown that sildenafilselective against PDE5 involved in the development of erections. Its activity against PDE5 is superior to that against other known phosphodiesterases. It is 10 times less effective against PDE6, which is involved in phototransmission in the retina. At the maximum recommended doses, it is 80 times less selective for PDE1 and 700 times less selective for PDEs 2, 3, 4, 7, 8, 9, 10, and 11. Sildenafil’s activity against PDE5 is about 4,000 times greater than its activity against PDES, cAMP, a specific phosphodiesterase involved in heart contraction.
Indications:
– Treatment of erectile dysfunction in men, which is manifested by the inability to achieve and maintain a penile erection sufficient to perform satisfactory sexual intercourse.
Sexual stimulation is necessary for the development of the® Vizarsin effect.
Dosage (Posology) and method of administration
For ingestion.
The recommended dose is 50 mg, which is taken as needed, about one hour before the expected sexual activity.
Depending on efficacy and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of administration of the drug is once daily. When taking Vizarsin® with food, the effect of the drug may develop later than when taken on an empty stomach.
Use in the elderly:
Elderly patients do not require a change in doses.
Use in patients with impaired renal function:
The dosage described in the section “Use in adults” is also applicable to patients with mild to moderate renal damage (creatinine clearance = 30-80 mL/min).
Since sildenafil clearance is reduced in patients with severe renal involvement (creatinine clearance <30 mL/min), the recommended dose is 25 mg. Depending on efficacy and tolerability, the dose may be increased to 50 mg or 100 mg.
Use in patients with impaired hepatic function:
Since the clearance of sildenafil is reduced in patients with hepatic lesions (e.g., cirrhosis), the recommended dose is 25 mg.
Use in people taking other medicines:
With the exception of ritonavir, for which concomitant use with sildenafil is not recommended, Vizarsin® is recommended at an initial dose of 25 mg in persons taking concomitant CYP3A4 inhibitors.
To reduce the likelihood of postural hypotension, it is necessary to achieve a stable state with alpha-blocker therapy before initiating Vizarsine® and the initial dose should be 25 mg.
Undesirable effects
Very common (≥ 1/10)
-headache
Common (≥1/100 to ≤ 1/10)
-vertigo
– Visual disturbances, color perception disorders (blurred vision, changes in sensitivity to light)
-Tides
– nasal congestion
-dyspepsia
Uncommon (≥1/1000 to ≤ 1/100)
– drowsiness, hypoesthesia
– conjunctiva, eye, tear disorders, etc.
Eye Disorders
– Dizziness, tinnitus
– palpitations, tachycardia
– Vomiting, nausea, dry mouth
-efflorescence
-myalgia
– Chest pain, general weakness
– Increased heart rate
Rare((≥1/10000 to ≤ 1/1000)
– Hypersensitivity reactions
– cerebrovascular events, syncope
-deafness*
– Myocardial infarction, atrial fibrillation
– Hypertension, hypotension
-nosebleed
* Ear disorders: sudden deafness. Sudden hearing loss or loss has been reported in a small number of cases during post-marketing use or in clinical trials of all PDE5 inhibitors, including sildenafil.
The following side effects have been identified during post-marketing surveillance and it is not known whether this is related to the use of the drug:
– Transient ischemic attacks, convulsions, recurrent convulsions
– Anterior ischemic optic neuropathy of non-arterial genesis
(NAION), retinal vascular occlusion, visual
field defects – ventricular arrhythmia, unstable angina pectoris
Contraindications
– hypersensitivity to sildenafil and other components of the drug;
– concomitant intake of nitric oxide donors,
organic nitrates or nitrites in any form
– Severe cardiovascular diseases (unstable angina pectoris
or severe heart failure)
– Reduced vision due to anterior ischemic optic
neuropathyne-arterial genesis (NAION) (regardless of whether
(i.e., whether or not it is associated with the use of PDE5 inhibitors)
– Severe liver damage
– hypotension (blood pressure <90>
– Recent stroke or infarction
– Established congenital degenerative retinal diseases
(retinitis pigmentosa, a congenital defect of retinal phosphodiesterases)
– Children under 18 years of age
Caution:
anatomical deformity of the penis (including angulation, cavernous fibrosis or Peyronie’s disease)
diseases that predispose to the development of priapism (such as sickle cell anemia, multiple myeloma, leukemia, thrombocythemia)
diseases accompanied by bleeding
exacerbation of peptic ulcer disease
Drug Interactions
Vizarsin® is a weak inhibitor of cytochrome P450-1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50>150μmol) inhibitors. When Vizarsin a is taken in recommended doses, its Cmax is about 1 μmol, so it is unlikely that Vizarsin®® can affect the clearance of substrates of these isoenzymes.
Vizarsin® enhances the hypotensive effect of nitrates both during long-term use of the latter and when they are prescribed for acute indications. In this regard, the use of Vizarsine® in combination with nitrates or nitric oxide donors is contraindicated.
There was no evidence of significant interaction with stolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9.
Vizarsine® (100 mg) has no effect on the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are CYP3A4 substrates, at constant blood levels. Vizarsine® (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).
Vizarsin® (50 mg) does not enhance the hypotensive effect of alcohol.
Concomitant use of Vizarsine with samlodipine® in patients with arterial hypertension did not show significant clinical interactions. The average additional reduction in blood pressure in the prone position is 8 mmHg. (systolic) and 7 mmHg. (diastolic).
Concomitant use of alpha-blocker doxazosin (4 mg) and
Vizarsine (25 mg) in patients with benign prostatic hyperplasia, both systolic and diastolic blood pressure in the supine® position is additionally reduced by an average of 7 mmHg. The use of higher doses of Vizarsin together with sdoxazosin® (4 mg) occasionally led to the development of orthostatic hypotension 1-4 hours after drug administration. In selected patients receiving alpha-adrenergic blockers, concomitant use of Vizarsin® may lead to symptomatic hypotension.
Vizarsin® enhances the anti-aggregation effect of sodium nitroprusside (nitric oxide donor).
Special warnings and precautions
To diagnose erectile dysfunction, determine their possible causes, and choose an adequate treatment, it is necessary to take a complete medical history and conduct a thorough physical examination.
Medications intended for the treatment of erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable. Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or strokes, life-threatening arrhythmias, arterial hypertension (BP >170/100 mm Hg) or hypotension (blood pressure < 90/50 mmHg) Rt. Art.
Vizarsin® 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, the risk of possible adverse vasodilating effects in patients with relevant diseases, especially in the context of sexual activity, should be carefully assessed before prescribing Vizarsin®. Increased susceptibility to quasodilators is observed in patients with left ventricular outflow obstruction (including aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with a rare syndrome of multiple systemic atrophy, manifested by severe dysregulation of blood pressure by the autonomic nervous system.
A small number of patients with hereditary retinitis pigmentosa have retinal phosphodiesterase disorders.There is no information on the safety of the use of Vizarsin in such patients, so Vizarsin®® should be used with caution in these patients.
Rare cases of non-arterial anterior ischemic optic neuropathy, which leads to visual impairment and blindness, have been reported with all PDE5 inhibitors, including Vizarsine® Most of these patients had risk factors such as age over 50 years, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. Physicians should inform patients who have undergone non-arterial anterior ischemic optic neuropathy of the increased risk of developing this disease. In case of unexpected deterioration or loss of vision, it is necessary to stop taking the drug and consult a doctor immediately.
In post-marketing and clinical studies, rare cases of sudden deterioration or loss of hearing have been reported with all PDE5 inhibitors, including Vizarsin®.
Most of these patients had risk factors for sudden deterioration or loss of hearing. A causal relationship between the use of PDE5 inhibitors and hearing impairment or loss has not been established. In case of sudden deterioration or loss of hearing, stop taking the drug and consult a doctor immediately.
The safety and efficacy of Vizarsine® in combination with other drugs intended for the treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended.
Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms
Against the background of taking Vizarsin, no negative effect on the ability to drive a car or other technical means was observed, however, since taking the drug may reduce blood pressure, the development of chromatopsia, blurred vision, you should be attentive to the individual effect of the drug in these situations,® especially at the beginning of treatment and when changing the dosage regimen.
Overdose
Symptoms: Increased side effects.
Treatment: symptomatic. Dialysis does not accelerate the clearance of sildenafil, as the latter actively binds to plasma proteins and is not excreted in the urine.
Dosage form and packaging
Film-coated tablets, 25 mg, 50 mg and 100 mg.
1, 2 or 4 tablets are placed in a blister made of polyvinyl chloride film and aluminum foil.
1 blister pack of 1, 2 or 4 tablets, or 2 blisters of 1, 2 or 4 tablets or 3 blister packs of 4 tablets together with the instructions for medical use in the state and Russian languages are placed in a cardboard pack.
Storage conditions
Store at a temperature not exceeding 30 °C.
Keep out of reach of children!
Shelf life
2 years.
Do not use after expiry of the retention period
Conditions of dispensing from pharmacies
By prescription
