MedED Solutions

Avanafil

Avanafil

Composition:

active ingredient: avanafil;

1 tablet contains 50 mg or 100 mg of avanafil;

excipients: mannitol (E 421), fumaric acid, hydroxypropyl cellulose, hydroxypropyl cellulose low-substituted, calcium carbonate, magnesium stearate, iron oxide yellow (E 172).

Dose form

Tablets.

Basic physical and chemical properties: tablets are round in shape, with a biconvex surface, light yellow in color. Almost white inclusions are allowed.

Pharmacotherapeutic group

Drugs for the treatment of erectile dysfunction.

ATC code G04B E10.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Avanafil is highly selective and potent a reversible inhibitor of phosphodiesterase type 5 (PDE5), specific to cyclic guanosine monophosphate (cGMP). When sexual stimulation causes local release of nitric oxide, PDE5 inhibition by avanafil results in an increase in cGMP levels in the corpus cavernosum of the penis. This promotes smooth muscle relaxation and blood flow to the tissues of the penis, which causes an erection. Avanafil has no effect in the absence of sexual stimulation. Pharmacodynamic effects

From in vitro studies, avanafil is known to be highly selective for PDE5. Its effect on PDE5 is more potent than other known phosphodiesterases (>100 times more potent than PDE6; >1000 times more potent than PDE4, PDE8 and PDE10; >5000 times more potent than PDE2 and PDE7 ; >10,000 times more potent than PDE1, PDE3, PDE9 and PDE11). Avanafil is >100 times more potent against PDE5 than against PDE6, which appears in the retina and is responsible for phototransformation. The selectivity of the effect to PDE5, which is approximately 20,000 times more potent than the effect to PDE3 (an enzyme found in the heart and blood vessels), is important given that PDE3 is involved in the control of myocardial contractility.

Pharmacokinetics.

Avanafil is rapidly absorbed after oral administration, with a median Tmax of 30 to 45 minutes. Its pharmacokinetics are dose-proportional over the recommended dose range. It is eliminated predominantly by hepatic metabolism (mainly via the CYP3A4 enzyme). Co-administration of potent inhibitors of CYP3A4 (eg, ketoconazole and ritonavir) is associated with an increase in the area under the concentration-time pharmacokinetic curve; (AUC) of avanafil in blood plasma (see section "Interaction with other medicinal products and other types of interactions"). The terminal half-life of Avanafil is approximately 6-17 hours.

Absorption. Avanafil is rapidly absorbed. The maximum plasma concentration (Cmax) is reached within 0.5-0.75 hours after oral administration on an empty stomach. When avanafil is taken with a high-fat meal, the rate of absorption decreases, with Tmax being slowed by an average of 1.25 hours and Cmax being reduced by an average of 39 % (when applying a dose of 200 mg). At the same time, there was no effect on the AUC value. Small changes in Cmax of avanafil are considered to be of minimal clinical significance.

Distribution. Avanafil is approximately 99% plasma protein bound. Protein binding does not depend on the total concentration of the active substance, age, kidney and liver function. Avanafil showed no accumulation in plasma when administered at a dose of 200 mg twice daily for 7 days. According to the results of determining the content of avanafil in the semen of healthy volunteers 45-90 minutes after taking the drug, less than 0.0002% of the dose taken may be in the semen of patients.

Biotransformation. Avanafil is excreted from the body mainly with the help of microsomal liver isoenzymes CYP3A4 (main route) and CYP2C9 (secondary route). The concentration of the main circulating metabolites — M4 and M16 — in plasma is approximately 23% and 29% of the concentration of the parent compound, respectively. The M4 metabolite has a phosphodiesterase selectivity profile similar to that of avanafil, and its in vitro PDE5 inhibitory activity is 18% of that of avanafil. Thus, M4 provides approximately 4% of the total pharmacological activity of the drug. Metabolite M16 was inactive against PDE5.

Excretion. Avanafil is extensively metabolized in humans. After oral administration, avanafil is excreted as metabolites, predominantly in the feces (approximately 63% of the oral dose), and to a lesser extent — urine (approximately 21% of the oral dose).

Other selected categories of patients

Older men. Older patients (65 years of age and older) had an exposure drug, comparable to the exposure observed in younger patients (18-45 years). However, data on persons over 70 years of age are still limited.

Impaired kidney function. In patients with mild (creatinine clearance ≥50–<80 ml/min) and moderate (creatinine clearance ≥30–<50 ml/min) renal dysfunction, the pharmacokinetics of avanafil did not change after a single dose of 200 mg . There are no data available for patients with severe renal dysfunction and patients with end-stage kidney disease receiving hemodialysis.

Hepatic dysfunction. After a single dose At the 200 mg dose, patients with mild hepatic dysfunction (Child-Pugh class A) had drug exposure comparable to that seen in individuals with normal liver function. Patients with moderate hepatic dysfunction (Child-Pugh class B) 4 hours after a single dose of avanafil 200 mg had drug exposure comparable to that observed in subjects with normal hepatic function. The maximum concentration and exposure were similar to those observed in subjects with normal liver function after taking avanafil at an effective dose — 100 mg.

Clinical characteristics

Indications

Treatment of erectile dysfunction in adult men.

Sexual stimulation is required for Avanafil to be effective.

Contraindications

Hypersensitivity to the active substance or to any of the excipients of the drug.

Simultaneous intake of any form of organic nitrates or nitric oxide donors (for example, amyl nitrite) (see section "Interaction with other drugs and others types of interactions".

The concomitant use of PDE5 inhibitors, including avanafil, with guanylate cyclase stimulants, such as riociguat, is contraindicated, as this can potentially lead to the development of symptomatic arterial hypotension (see section "Interaction with other drugs and other interactions).

Physicians should weigh the potential risk of sexual activity to cardiac function in patients with cardiovascular disease before prescribing Avanafil.

The use of avanafil is contraindicated in the following categories of patients:

  • patients who have had a myocardial infarction, stroke or life-threatening arrhythmia within the last 6 months;
  • patients with arterial hypotension  (blood pressure <90/50 mmHg) or arterial hypertension (blood pressure >170/100 mmHg) at rest;
  • patients with unstable angina, angina with sexual activity or congestive heart failure, New York Heart Association functional class 2 or higher.

Severe hepatic impairment (Child–Pugh class C).

Severe renal impairment (creatinine clearance < 30 ml/min).

Vision loss in one eye due to non-arterial anterior ischemic optic neuropathy (NAION), regardless of whether this case was related to previous use PDE5 inhibitors (see section "Peculiarities of use").

Hereditary degenerative disease of the retina.

Concomitant use of potent inhibitors of CYP3A4, such as ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin (see sections "Interaction with other drugs and other types of interactions", "Peculiarities of application"; and "Method of administration and dosage").

Interaction with other medicinal products and other forms of interaction

Potential pharmacodynamic interactions with avanafil

Nitrates. In healthy volunteers, avanafil is known to enhance the hypotensive effects of nitrates compared to placebo. This is thought to be due to the combined effects of nitrates and avanafil on the nitric oxide/cGMP mechanism. In this regard, the appointment of avanafil in patients who take any form of organic nitrates or nitric oxide donors (for example, amyl nitrite) is contraindicated. In a patient who has taken avanafil in the last 12 hours, medically warranted use of nitrates in a life-threatening condition increases the likelihood of a significant and potentially dangerous decrease in blood pressure. Even in such circumstances, nitrates should only be used under close medical supervision and with proper hemodynamic monitoring (see section "Contraindications").

Medicines that lower systemic blood pressure. As a vasodilator, avanafil may lower systemic blood pressure. When Avanafil is used in combination with another drug that lowers systemic blood pressure, the additive effects may lead to symptomatic hypotension (eg, dizziness, feeling light-headed, syncope or a state close to syncope). There is information that in the course of clinical studies there were no cases of development of arterial hypotension, however, individual episodes of dizziness were noted (see section "Adverse reactions"). During these studies, one episode of syncope was reported in the placebo group and one episode of syncope in the avanafil 100 mg group.

Patients with left ventricular outflow tract obstruction (eg, aortic stenosis, idiopathic hypertrophic stenosis) and patients with severe disorders of autonomic control of blood pressure may be particularly sensitive to the action of vasodilators, including avanafil.

Alpha-blockers. There is information that hemodynamic drug interactions with doxazosin and tamsulosin were studied in healthy volunteers in one crossover study with two periods. In patients receiving stable doxazosin therapy, the mean maximum reduction in standing and supine systolic blood pressure (adjusted for placebo) after taking avanafil was 2.5 mmHg. Art. and 6.0 mm Hg. Art. respectively. Overall, 7 out of 24 study participants after taking avanafil showed levels of reduction in this indicator from baseline values that were of potential clinical significance (see section "Peculiarities of use").

It is known that in patients, receiving stable therapy with tamsulosin, the average maximum reduction in systolic blood pressure in the standing and supine position (adjusted for placebo) after taking avanafil was 3.6 mm Hg. Art. and 3.1 mm Hg. Art. respectively, and 5 of 24 study participants after taking avanafil had levels of reduction in this indicator from baseline values that were of potential clinical significance (see section "Peculiarities of use").

None of the groups of participants there were no reports of syncope or other severe adverse events associated with a decrease in blood pressure in the study.

Other antihypertensive drugs other than alpha-blockers. Known to evaluate the effect of avanafil on potentiation the effects of individual antihypertensive drugs (amlodipine and enalapril) on lowering blood pressure was conducted in a clinical study. The results of the study showed that with the simultaneous use of avanafil, the average maximum decrease in blood pressure in the supine position was 2/3 mm Hg. Art. compared with placebo in the enalapril group and 1/-1 mm Hg. Art. — in the amlodipine group.

A statistically significant difference in the maximum decrease in diastolic blood pressure in the supine position compared with placebo was observed only in the combined use of enalapril and avanafil, while the level of blood pressure reduction returned to baseline values 4 hours after taking a dose of avanafil. In both groups, there was one patient each who had a decrease in blood pressure without symptoms of arterial hypotension, which was eliminated within 1 hour after the onset. Avanafil had no effect on the pharmacokinetics of amlodipine, however, amlodipine increased the maximum and total exposure of avanafil by 28% and 60%, respectively.

Alcohol. Drinking alcohol in combination with avanafil increases the risk development of symptomatic arterial hypotension. There is information that in one cross-sectional study in which healthy volunteers received a single dose of the drug, the mean maximum decrease in diastolic blood pressure was statistically significantly greater after taking avanafil with alcohol than after taking avanafil alone (by 3.2 mm Hg. Art.) or alcohol alone (by 5.0 mmHg) (see section "Peculiarities of use").

Other treatments for erectile dysfunction. Safety and efficacy of Avanafil in combination with other PDE5 inhibitors or with other drugs for the treatment of erectile dysfunction have not been studied (see section "Peculiarities of use").

The effect of other substances on avanafil

Avanafil is a substrate of CYP3A4 and metabolized by this enzyme. It is known from studies that drugs that inhibit CYP3A4 may increase the AUC of avanafil.

CYP3A4 inhibitors. Ketoconazole (400 mg daily), which is a selective and very potent inhibitor of CYP3A4 , increased the Cmax and AUC of avanafil after a single dose of 50 mg by 3-fold and 14-fold, respectively, and extended the elimination half-life of avanafil to approximately 9 hours. Ritonavir (600 mg twice daily), which is a very potent inhibitor of CYP3A4 and also inhibits CYP2C9, increased Cmax and AUC of avanafil after a single dose of 50 mg approximately 2-fold and 13-fold respectively, and extended the half-life of avanafil to approximately 9 hours. Other potent inhibitors of CYP3A4 (eg, itraconazole, voriconazole, clarithromycin, nefazodone, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin) are expected to cause similar effects. Thus, the simultaneous use of avanafil with potent inhibitors of CYP3A4 is contraindicated (see sections "Contraindications", "Peculiarities of use" and "Method of administration and dosage").

Erythromycin (500 mg 2 times a day ), which is a moderate inhibitor of CYP3A4, increased the Cmax and AUC of avanafil after a single dose of 200 mg approximately 2-fold and 3-fold, respectively, and extended the half-life of avanafil to approximately 8 hours. Other mild inhibitors of CYP3A4 (eg, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, and verapamil) are expected to cause similar effects. In this regard, for patients who are simultaneously taking moderate inhibitors of CYP3A4, the maximum recommended dose of avanafil is 100 mg every 48 hours (see section "Dosage and Administration").

Although there are no interactions with specific drugs studied, other CYP3A4 inhibitors, including grapefruit juice, are likely to increase the AUC of avanafil. Patients should be warned against drinking grapefruit juice within 24 hours prior to taking avanafil.

CYP3A4 substrate. Amlodipine (5 mg daily) increased Cmax and The AUC of avanafil after a single dose of 200 mg was approximately 28% and 60%, respectively. These changes in AUC are not considered clinically significant. A single dose of avanafil did not affect plasma levels of amlodipine.

Although interactions of avanafil with rivaroxaban and apixaban (both CYP3A4 substrates) have not been specifically studied, such interactions are not expected.

CYP450 enzyme inducers. The potential effect of CYP enzyme inducers, especially CYP3A4 inducers (eg, bosentan, carbamazepine, efavirenz, phenobarbital, and rifampicin), on the pharmacokinetics and efficacy of avanafil has not been studied. Simultaneous use of avanafil and CYP enzyme inducers is not recommended as this may reduce the effectiveness of avanafil.

Influence of avanafil on other medicinal products

Inhibition of cytochrome P450 enzymes. C In in vitro studies, it is known that avanafil (on human liver microsomes) has shown little potential for drug interactions mediated by CYP1A1/2, 2A6, 2B6 and 2E1 enzymes. In addition, avanafil metabolites (M4, M16 and M27) also showed minimal inhibition of CYP enzymes 1A1/2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. Given these data, avanafil is not expected to have a significant effect on other drugs that are metabolized by these enzymes.

Although data from in vitro studies have identified potential interactions of avanafil mediated enzymes CYP 2C19, 2C8/9, 2D6 and 3A4, further studies using omeprazole, rosiglitazone and desipramine did not reveal clinically significant interactions mediated by CYP 2C19, 2C8/9 and 2D6 enzymes.

Enzyme induction cytochrome P450. Evaluation of the potential to induce CYP1A2, CYP2B6 and CYP3A4 enzymes by avanafil, which was performed on primary human hepatocytes in in vitro studies, did not reveal any potential to induce these enzymes at clinically relevant concentrations. p>

Transporters. Results from in vitro studies have demonstrated a modest potential for avanafil as a P-glycoprotein (P-gp) substrate and P-gp inhibitor together with digoxin as substrate in concentrations below the calculated concentrations in the intestine. The potential of avanafil to interfere with P-gp mediated transport of other drugs is unknown.

Based on in vitro studies, avanafil, when used at clinically relevant concentrations, may act as an inhibitor of BCRP (resistance protein breast cancer). At clinically relevant concentrations, avanafil is not an inhibitor of the transport proteins OATP1B1, OATP1B3, OCT1, OCT2, OAT1, OAT3 and BSEP.

The effect of avanafil on other transporters is not yet known.

Riociguat . There is information that preclinical studies have demonstrated an additive effect in lowering systemic blood pressure when using PDE5 inhibitors in combination with riociguat. In clinical studies, riociguat has been shown to enhance the hypotensive effects of PDE5 inhibitors. Evidence was not obtained in favor of a favorable clinical effect of the use of this combination in the study populations. The concomitant use of riociguat and PDE5 inhibitors, including avanafil, is contraindicated (see section "Contraindications").

Peculiarities of use.Before prescribing medication, a medical history and a general physical examination should be taken to diagnose erectile dysfunction and determine its possible primary causes.

Cardiovascular function. Before Before starting any therapy for erectile dysfunction, the physician should evaluate the cardiovascular status of their patients, since sexual activity poses a certain risk to cardiac function (see section "Contraindications"). Avanafil has vasodilatory properties, which leads to a slight temporary decrease in blood pressure (see the section "Interaction with other medicinal products and other types of interactions") and potentiates the hypotensive effect of nitrates (see the section "Contraindications"). Patients with left ventricular outflow tract obstruction, such as aortic valve stenosis or idiopathic hypertrophic subaortic stenosis, may be sensitive to the effects of vasodilators, including PDE5 inhibitors.

Priapism. Patients should be instructed to seek immediate medical attention if an erection lasts 4 hours or more (priapism). If priapism is not properly treated promptly, penile tissue damage and irreversible loss of potency can occur. Avanafil should be used with caution in patients with an anatomical deformity of the penis (such as angulation, cavernous fibrosis or Peyronie's disease) and in patients with diseases that can lead to the development of priapism (such as sickle cell anemia, multiple myeloma or leukemia).

Visual impairment. In connection with the use of other PDE5 inhibitors, visual impairment and cases of anterior ischemic optic neuropathy of non-arterial origin have been reported. The patient should be advised that in the event of a sudden deterioration in vision, it is necessary to stop using the drug Avanalav ® and immediately consult a doctor (see section "Contraindications"). p>

Influence on blood clotting. In vitro studies on human platelets indicate that PDE5 inhibitors do not affect platelet aggregation by themselves, but in supratherapeutic doses they potentiate the antiplatelet effect of the sodium nitric oxide donor nitroprusside. In humans, PDE5 inhibitors do not affect clotting time either as monotherapy or when used with acetylsalicylic acid.

Information on the safety of using avanafil in patients with impaired blood coagulation or with active peptic ulcer of the stomach is not available. Therefore, avanafil should only be used in these patients after a careful benefit/risk assessment.

Worsening or sudden hearing loss. Patients should be advised to stop taking PDE5 inhibitors, including including avanafil, and seek immediate medical attention in the event of a sudden deterioration or loss of hearing. These events, which may be accompanied by tinnitus/ringing and dizziness, have been reported as time-related to PDE5 inhibitors. It is not possible to establish whether there is a direct relationship between these phenomena and the use of PDE5 inhibitors or other factors.

Concomitant use of alpha-blockers. Concomitant use of alpha-blockers and avanafil may result in some patients to symptomatic arterial hypotension through additive vasodilating effects (see section "Interaction with other drugs and other types of interactions"). The following should be considered:

  • Before initiating treatment with Avanafil, the condition of a patient undergoing alpha-blocker therapy should be stabilized. Patients who demonstrate hemodynamic instability on alpha-blocker monotherapy have an increased risk of developing symptomatic hypotension while taking avanafil.
  • For those patients who are stable on alpha-blocker therapy, avanafil therapy should be start with the lowest dose — 50 mg
  • For those patients who are already taking an optimized dose of Avanafil, alpha-blocker therapy should be initiated at the lowest dose. Gradually increasing the dose of an alpha-blocker while taking avanafil may be accompanied by an additional decrease in blood pressure.
  • Other factors, including a decrease in circulating blood volume and the use of other antihypertensive drugs, may affect the safety of the combined use of avanafil and alpha-blockers. medicinal products.

Concomitant use of CYP3A4 inhibitors. Concomitant use of avanafil with potent CYP3A4 inhibitors such as ketoconazole or ritonavir is contraindicated (see sections Contraindications, "Interaction with other drugs and other types of interactions" and "Method of administration and doses".

Concomitant use of other drugs for the treatment of erectile dysfunction. The safety and efficacy of Avanafil in combination with other PDE5 inhibitors or with other drugs for the treatment of erectile dysfunction have not been studied. Patients should be warned against taking Avanafil in combination with these medicinal products.

Concomitant alcohol use. Alcohol use in combination with the use of avanafil increases the risk of developing symptomatic arterial hypotension (see section "Interaction with other medicinal products and other types of interactions"). Patients should be cautioned that the concomitant use of avanafil and alcohol increases the likelihood of hypotension, dizziness, or syncope. Physicians should also instruct patients on what to do if symptoms of postural hypotension occur.

Populations in which the drug has not been studied. Avanafil has not been studied in patients with erectile dysfunction due to spinal cord injury or other neurological disorder, and in patients with severe renal or hepatic impairment.

Use during pregnancy or lactation.

Pregnancy. Avanafil is not intended for use by women.

The use of avanafil in pregnant women is not recommended. The results of animal studies do not indicate the existence of any direct or indirect harmful effect of the drug on the course of pregnancy, development of the embryo / fetus, childbirth or postnatal development of offspring.

The period of breastfeeding. There are no data on the use of avanafil during breastfeeding.

Fertility. After a single oral dose of avanafil at a dose of 200 mg in healthy volunteers, no effect on sperm motility or morphology was observed. Currently, there are no data on spermatogenesis in healthy adult men and in adult men with mild erectile dysfunction.

The ability to influence the reaction rate when driving vehicles or operating other mechanisms.< /strong>

The drug Avanafil has a slight effect on the ability to drive and use machines. Dizziness and visual disturbances have been reported in clinical trials with avanafil, so patients should be aware of how they react to Avanafil before driving or work with machinery.

Method of administration and dosage

Dosage

The recommended dose is 100 mg, which is taken, if necessary, approximately 15-30 minutes before sexual activity. Given individual efficacy and tolerability, the dose can be increased to a maximum — 200 mg or reduce to 50 mg. The maximum recommended frequency of application — 1 time per day. Sexual stimulation is needed to get a response to treatment.

Special categories of patients

Older males (≥65 years). For older patients, dose adjustment is not required. Regarding the use of the drug in patients over the age of 70 years, the available data are still limited.

Impaired renal function. Dose adjustment for patients with mild to moderate renal dysfunction (creatinine clearance ≥30 ml/ min) is not required. The drug Avanafil is contraindicated in patients with severe renal dysfunction (creatinine clearance

In patients with mild or moderate renal dysfunction (creatinine clearance ≥30 ml / min, but <80 ml/min) there was a decrease in the effectiveness of the drug compared with patients with normal renal function.

Impaired liver function.

Avanafil is contraindicated in patients with severe hepatic dysfunction (Child-Pugh class C) Contraindications". In patients with mild or moderate hepatic dysfunction (Child-Pugh class A or B), treatment with the drug should be started at the lowest effective dose, with subsequent adjustment, taking into account tolerability.

Use for men with diabetes. For patients with diabetes, dose adjustment is not required.

Use in patients taking other drugs

Concomitant use of CYP3A4 inhibitors.

Co-administration of Avanafil with potent inhibitors of CYP3A4 (such as ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, and telithromycin) is contraindicated (see section 4.4). sections "Contraindications", "Interaction with other medicinal products and other types of interactions"; and "Peculiarities of use".

For patients who receive concomitant treatment with moderate inhibitors of CYP3A4 (such as erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fozamprenavir and verapamil), the maximum recommended dose of avanafil is 100 mg , and at the same time it is necessary to observe the interval between doses of at least 48 hours (see the section "Interaction with other drugs and other types of interactions").

Method of application

For oral administration. If Avanafil is taken with food, the onset of action may be later than when taken on an empty stomach (see section "Pharmacological properties. Pharmacokinetics").

Children.

Do not use in children (under 18 years of age).

Overdose

In cases of overdose, if necessary, standard supportive measures should be taken. Hemodialysis is not expected to accelerate the clearance of avanafil because avanafil is highly protein bound and not excreted in the urine. in multiple doses up to 300 mg per day. Adverse reactions were similar to those observed at lower doses, but their frequency and severity increased.

Adverse reactions

The adverse reactions below are classified by organ system (according to MedDRA) and by frequency of occurrence: very often (≥1/10); often (≥1/100–<1/10); infrequently (≥1/1000<1/100); rarely (≥1/10000<1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data).

Immune system disorders: rare — seasonal allergies.

On the part of the psyche: rarely — insomnia, premature ejaculation, inadequate affect.

On the part of the nervous system: often — headache; infrequently — dizziness, drowsiness, sinus headache; rarely — psychomotor hyperactivity.

On the part of the organs of vision: infrequently — blurred vision.

On the part of the heart: infrequently — increased heartbeat; rarely — angina pectoris, tachycardia.

On the part of the vessels: often — hyperemia; infrequently — hot flushes, arterial hypertension.

On the part of the respiratory system, chest organs and mediastinum: often — stuffy nose; infrequently — sinuses are laid, shortness of breath during physical exertion; rarely — rhinorrhea, congestion in the upper respiratory tract, epistaxis (nosebleed).

From the gastrointestinal tract: infrequently — dyspepsia, nausea, vomiting, stomach discomfort; rarely — dry mouth, gastritis, pain in the lower abdomen, diarrhea.

On the part of the skin and subcutaneous tissue: rarely — rash.

On the part of the musculoskeletal system and connective tissue: infrequently — back pain, muscle tension; rarely — pain in the side, myalgia, muscle spasms.

On the part of the kidneys and urinary tract: rarely — pollakiuria.

On the part of the reproductive system and mammary glands: rarely — penile disorders, spontaneous penile erection, genital itching.

Infectious and parasitic diseases: rare — flu, nasopharyngitis.

Metabolic and alimentary disorders: rare — gout.

General disorders and reactions at the injection site: infrequently — increased fatigue; rarely– general weakness, chest pain, influenza-like illness, peripheral edema.

Laboratory values: infrequently — increased levels of liver enzymes, abnormalities on the electrocardiogram, increased heart rate; rarely — increased blood pressure, blood in urine, heart murmur, increased prostate-specific antigen, weight gain, increased blood bilirubin, increased blood creatinine, increased body temperature.

Reporting Suspected Adverse Reactions

This medicinal product is subject to additional monitoring. This will allow you to quickly identify new security information. Reporting suspected adverse reactions after drug approval by regulatory authorities is an important procedure. This allows for continuous monitoring of the benefit/risk ratio of this medicinal product. Health care professionals are requested to report all suspected adverse reactions through the national reporting system.

Expiry date

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 oC.

Keep out of the reach of children.

Packing

1 tablet in a blister; 1 blister in a pack.

4 tablets in a blister; 1 blister per pack.

Dispensation category

Prescription.

 

Comparison