Pinap tablets 10 mg No. 4

Instructions for Pinap tablets 10 mg No. 4

Composition

active ingredient: tadalafil;

1 tablet contains 2.5 mg or 5 mg, or 10 mg, or 20 mg of tadalafil;

excipients: tablet core: lactose monohydrate, croscarmellose sodium, sodium lauryl sulfate, hydroxypropylcellulose, polysorbate 80, magnesium stearate;

tablet shell:

for 2.5 mg tablets: ready-to-use mixture [hypromellose, lactose monohydrate, titanium dioxide (E 171), triacetin, talc, iron oxide yellow (E 172), iron oxide red (E 172)];

for 5 mg tablets: ready-to-use mixture [hypromellose, lactose monohydrate, titanium dioxide (E 171), triacetin, talc, iron oxide yellow (E 172)];

for 10 mg tablets: ready-to-use mixture [hypromellose, lactose monohydrate, titanium dioxide (E 171), triacetin, talc, iron oxide yellow (E 172), iron oxide black (E 172)];

for 20 mg tablets: ready-to-use mixture [hypromellose, lactose monohydrate, titanium dioxide (E 171), triacetin, talc, iron oxide yellow (E 172)].

Dosage form

Film-coated tablets.

Main physicochemical properties: film-coated tablets, caplet-shaped, biconvex; 2.5 mg tablets: yellow-orange, with the inscription "T 2" on one side; 5 mg tablets: yellow, with the inscription "T 5" on one side; 10 mg tablets: yellow, with the inscription "T 10" on one side; 20 mg tablets: yellow, with the inscription "T 20" on one side.

Pharmacotherapeutic group

Drugs for the treatment of erectile dysfunction. ATC code G04B E08.

Pharmacological properties

Pharmacodynamics.

Mechanism of action.

Tadalafil is a selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP) - a specific phosphodiesterase type 5 (PDE 5). When sexual stimulation causes local release of nitric oxide, inhibition of PDE 5 by tadalafil produces increased levels of cGMP in the corpus cavernosum. This leads to relaxation of smooth muscle and blood flow to the tissues of the penis, thereby creating an erection. Tadalafil does not show its effect in the treatment of erectile dysfunction in the absence of sexual stimulation.

The inhibitory effect on the concentration of cGMP in the corpus cavernosum is also observed in the smooth muscles of the prostate, the urinary bladder and their vessels that carry blood to the above organs. The vascular relaxation that occurs in this case causes an increase in blood perfusion and may be responsible for the reduction of symptoms of benign prostatic hyperplasia. These vascular effects may be supplemented by inhibition of the activity of the bladder afferent nerves and relaxation of the smooth muscles of the prostate and bladder.

Pharmacodynamic effects.

In vitro studies have shown that tadalafil is a selective inhibitor of PDE5. PDE5 is an enzyme found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung and cerebellum. Tadalafil has a stronger effect on PDE5 than on other phosphodiesterases. Tadalafil is 10,000 times more potent on PDE5 than on PDE1, PDE2 and PDE4, which are present in the heart, brain, blood vessels, liver and other organs. Tadalafil is 10,000 times more potent on PDE5 than on PDE3, an enzyme present in the heart and blood vessels. This selectivity for PDE5 over PDE3 is important because PDE3 is an enzyme that plays a role in cardiac muscle contraction. In addition, tadalafil is approximately
700 times more potent against PDE 5 compared to PDE 6, which is an enzyme found in the retina and responsible for phototransduction. Tadalafil is also 10,000 times more potent against PDE 5 compared to PDE 7, PDE 8, PDE 9 and PDE 10.

Clinical efficacy and safety.

Tadalafil administered to healthy volunteers did not show any significant difference compared to placebo in terms of systolic and diastolic blood pressure in the supine position (mean maximum decrease 1.6/0.8 mmHg, respectively), systolic and diastolic blood pressure in the standing position (mean maximum decrease 0.2/4.6 mmHg, respectively), and significant change in heart rate.

In a study of the effects of tadalafil on vision using the Farnsworth-Munsell 100 Hue color perception test, tadalafil did not impair color perception (blue/green). Clinical study data support the low affinity of tadalafil for PDE6 compared to PDE5. In all clinical studies, changes in color perception were rarely (< 0.1%) reported.

Three clinical studies were conducted in men to evaluate the potential effects of Pinapu on spermatogenesis at a dose of 10 mg (one study of 6 months duration) and at a dose of 20 mg (one study of 6 months duration and one of 9 months duration) at a dose frequency of 1 time / day. In two of the three studies, a clinically insignificant decrease in sperm count and concentration was observed associated with the use of tadalafil. These effects were not associated with changes in other characteristics, such as sperm motility, morphology and blood levels of follicle-stimulating hormone.

Erectile dysfunction.

In a 12-week study of 186 patients (142 patients receiving tadalafil, 44 patients receiving placebo) with erectile dysfunction secondary to spinal cord injury, tadalafil showed significant improvement in erectile function, and the average success rate with Pinapu 10 mg or 20 mg (dose titration, as needed) was 48% compared to 17% in the placebo group.

Tadalafil 2.5 mg, 5 mg and 10 mg once daily were evaluated in 3 clinical trials in 853 patients of various ages (21 to 82 years) and ethnicities with erectile dysfunction of varying severity (mild, moderate, severe) and etiology. In the two primary efficacy trials in the general population, the average success rate was 57% and 67% for Pinapu 5 mg and 50% for Pinapu 2.5 mg compared with 31% and 37% for placebo. In the trials in patients with erectile dysfunction secondary to diabetes, the average success rate was 41% and 50% for Pinapu 2.5 mg and 50% for Pinapu 2.5 mg, respectively.
46% with Pinapu 5 mg and 2.5 mg, respectively, compared with 28% in the placebo group. Most patients in the above studies had previously taken PDE5 inhibitors on an as-needed basis. In a subsequent study, 217 patients who had not previously taken PDE5 inhibitors
PDE5, received Pinap 5 mg once daily and placebo. The average success rate was 68% in the Pinap group compared to 52% in the placebo group.

Benign prostatic hyperplasia.

The use of Pinapu was studied in four clinical trials lasting
12 weeks, involving 1500 patients with symptoms of benign prostatic hyperplasia. In these clinical studies, Pinap at a dose of 5 mg demonstrated an improvement in the patient's condition on the International Prostatic Symptom Score (IPSS) compared to placebo (IPS improvement scores for Pinap at a dose of 5 mg are -4.8, -5.6, -6.1 and -6.3, compared to -2.2, -3.6 -3.8, -4.2 in the case of placebo). Improvement in the patient's condition on the International Prostatic Symptom Score (IPSS) was observed after 1 week of treatment. In one of the clinical studies, which also included tamsulosin at a dose of 0.4 mg as an active comparator, the IPS improvement scores for Pinap at a dose of 5 mg, tamsulosin and placebo were -6.3, -5.7 -4.2, respectively.

One of these studies assessed both the improvement in erectile function and the reduction in symptoms of benign prostatic hyperplasia in patients with both conditions. The improvement in erectile function on the International Index of Erectile Function and the International Prostatic Symptom Score was -6.5 and -6.1 for Pinapu 5 mg compared with -1.8 and -3.8 for placebo, respectively. The average percentage of successful sexual intercourse attempts per person in the study was 71.9% for Pinapu 5 mg and 48.3% for placebo.

Maintenance of the achieved effect of Pinapu was assessed in an additional open-label study, the results of which showed that the improvement in the total international prostatic symptom score observed over 12 weeks was maintained for up to 1 year after treatment with Pinapu at a dose of 5 mg.

Children.

One study in children with Duchenne muscular dystrophy (DMD) has been conducted, and no conclusive evidence of efficacy has been demonstrated. This efficacy study of tadalafil was a randomized, double-blind, placebo-controlled, three-arm, parallel-group study in 331 male children aged 7 to 14 years with DMD who were receiving concomitant corticosteroid therapy. The study included a 48-week double-blind period during which patients were randomized to receive tadalafil 0.3 mg/kg, tadalafil 0.6 mg/kg, or placebo daily. Tadalafil did not demonstrate efficacy in the primary endpoint of slowing the decline in walking speed as measured by the change in distance in the 6-minute walk test (6MWT). The least squares mean change in TLC distance at week 48 was 51.0 m in the placebo group compared to 64.7 m in the tadalafil 0.3 mg/kg group (p=0.307) and 59.1 m in the tadalafil 0.6 mg/kg group (p=0.538). No evidence of efficacy was found in the re-analysis of the results of this study. The overall safety findings from this study were generally consistent with the known safety profile of tadalafil and the adverse events expected in the pediatric DMD population when treated with corticosteroids.

Pharmacokinetics.

Absorption. Tadalafil is well absorbed after oral administration. The mean maximum plasma concentration (Cmax) is reached on average 2 hours after administration. The absolute bioavailability of tadalafil after oral administration has not been established.

The rate and extent of absorption of tadalafil are independent of food intake, so Pinap can be taken with or without food. The time of administration (morning or evening) had no clinically significant effect on the rate and extent of absorption.

Less than 0.0005% of the administered dose was detected in the semen of healthy volunteers.

Metabolism: Tadalafil is primarily metabolized by the cytochrome P450 (CYP) 3A4 isoform. The major circulating metabolite is methylcatechol glucuronide. This metabolite has 13,000-fold less activity against PDE5 than tadalafil. Therefore, the metabolite is not expected to be clinically active at the concentrations observed.

Elimination: The mean oral clearance of tadalafil is 2.5 L/h and the mean elimination half-life is 17.5 hours in healthy subjects. Tadalafil is excreted primarily as inactive metabolites, primarily in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).

Linearity/non-linearity of pharmacokinetics. The pharmacokinetics of tadalafil in healthy volunteers are linearly proportional to time and dose. In the dose range of 2.5 mg to 20 mg, exposure (AUC) increases proportionally to dose. Steady-state plasma concentrations are achieved within 5 days of once-daily dosing.

The pharmacokinetics of the drug are the same in patients with and without erectile dysfunction.

Certain population groups.

Elderly: Healthy elderly volunteers (65 years and older) had lower oral tadalafil clearance values, resulting in an increase in
25% of exposure (AUC) compared to healthy volunteers aged 19–45 years. This age effect is not clinically relevant and does not require dose adjustment.

Renal impairment: In clinical pharmacology studies with single doses of tadalafil (5-20 mg), tadalafil AUC exposure was approximately doubled in patients with mild (creatinine clearance 51 to 80 mL/min) or moderate (creatinine clearance 31 to 50 mL/min) renal impairment, as well as in patients with end-stage renal disease on dialysis. In patients on hemodialysis, the maximum plasma concentration (Cmax) was 41% higher than in healthy volunteers.

The effect of hemodialysis on the elimination of tadalafil can be neglected.

Hepatic impairment. Tadalafil exposure (AUC) in patients with mild to moderate hepatic impairment (Child-Pugh class A and B) is comparable to that in healthy volunteers given a 10 mg dose. There are limited data on the safety of Pinapu in patients with severe hepatic impairment (Child-Pugh class C). There are no data on the use of Pinapu once daily in patients with hepatic impairment. The physician should carefully assess the individual benefits/risks of prescribing Pinapu once daily.

Patients with diabetes mellitus: Tadalafil exposure (AUC) in diabetic patients was approximately 19% lower than AUC in healthy volunteers. This difference in exposure does not require dose adjustment.

Indication

For dosages of 2.5 mg, 10 mg, 20 mg. Treatment of erectile dysfunction in adult men. The drug is effective in the presence of sexual stimulation.

For a dosage of 5 mg. Treatment of erectile dysfunction in adult men. The drug is effective for the treatment of erectile dysfunction in the presence of sexual stimulation.

Treatment of symptoms of benign prostatic hyperplasia in adult men.

Pinup is not indicated for use by women.

Contraindication

Hypersensitivity to tadalafil or any other component of the drug.

In clinical studies, tadalafil has been shown to potentiate the hypotensive effect of nitrates. This is thought to be a result of the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway. Therefore, tadalafil is contraindicated in patients taking organic nitrates in any dosage form (see section 4.5).

Pinap should not be used in men with heart disease for whom sexual activity is undesirable. Physicians should consider the potential cardiac risk of sexual activity in patients with a history of cardiovascular disease.

The following groups of patients with cardiovascular disease were not included in clinical trials, therefore the use of tadalafil is contraindicated for them:

• patients with myocardial infarction within the last 90 days;
• patients with unstable angina or angina occurring during sexual intercourse;
• patients with heart failure corresponding to class 2 or higher according to the New York Heart Association classification, within the last 6 months;
• patients with uncontrolled arrhythmias, hypotension (< 90/50 mm Hg) or uncontrolled hypertension;
• patients after a stroke that occurred within the last 6 months.

Pinap is contraindicated in patients with loss of vision in one eye as a result of non-arteritic anterior ischemic optic neuropathy (NAPION), regardless of whether this was related to previous exposure to PDE5 inhibitors (see section "Special warnings and precautions for use").

Concomitant use of PDE5 inhibitors, including tadalafil, with guanylate cyclase stimulators such as riociguat is contraindicated as it may potentially lead to symptomatic hypotension (see section 4.5).

Interaction with other medicinal products and other types of interactions

Interaction studies were performed at 10 mg and 20 mg doses, and the data are presented below. In the interaction studies that used only Pinap 10 mg, a clinically significant interaction at higher doses cannot be excluded.

Effects of other drugs on tadalafil.

Cytochrome CYP450 inhibitors.

Tadalafil is metabolized primarily by CYP3A4. Ketoconazole (200 mg daily), a selective CYP3A4 inhibitor, increased the area under the concentration-time curve (AUC) of tadalafil (10 mg) by 2-fold and Cmax by 15% relative to the AUC and Cmax of tadalafil alone. Ketoconazole (400 mg daily) increased the area under the concentration-time curve (AUC) of tadalafil (20 mg) by 4-fold and Cmax by 22%. Ritonavir, a protease inhibitor (200 mg twice daily) that inhibits CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased the area under the concentration-time curve (AUC) of tadalafil (20 mg) by 2-fold without changing Cmax. Although specific interactions have not been studied, other protease inhibitors such as saquinavir and other CYP3A4 inhibitors such as erythromycin, clarithromycin, itraconazole and grapefruit juice should be administered with caution as they are expected to increase tadalafil plasma concentrations when co-administered (see section 4.4). As a result, the incidence of adverse reactions may be increased.
(see section "Adverse reactions").

Transporters.

The effect of transporters, such as p-glycoprotein, on the disposition of tadalafil is unknown. Thus, there is a possibility of drug interactions mediated by transporter inhibition.

Cytochrome CYP450 inducers.

The CYP3A4 inducer rifampicin reduced the AUC of tadalafil by 88% compared to the AUC of tadalafil alone (10 mg). It can be assumed that this reduction in concentration will lead to a decrease in the efficacy of tadalafil; the extent of the decrease in efficacy is unknown. Concomitant use of other CYP3A4 inducers, such as phenobarbital, phenytoin and carbamazepine, may also reduce the plasma concentration of tadalafil.

The effect of tadalafil on other drugs.

Nitrates. In clinical studies, tadalafil (5 mg, 10 mg, 20 mg) has been shown to potentiate the hypotensive effects of nitrates. Therefore, the use of Pinap in patients receiving treatment with organic nitrates in any form is contraindicated (see section "Contraindications"). According to the results of a clinical study involving 150 patients who used tadalafil at a dose of 20 mg per day for 7 days and nitroglycerin at a dose of 0.4 mg sublingually (with different times of administration), this interaction lasted for more than 24 hours and was not detected after 48 hours after the last dose of tadalafil. Therefore, if the use of nitrates is medically necessary for a patient who is prescribed Pinap at any dose (2.5–20 mg) in a life-threatening condition, then at least 48 hours should elapse after the last dose of Pinap. In this case, the use of nitrates should be under close medical supervision with appropriate monitoring of hemodynamic parameters.

Antihypertensive drugs (including calcium channel blockers).

During the co-administration of tadalafil (at a dosage of 5 mg once daily or as a single dose of 20 mg) with the α-adrenoceptor blocker doxazosin (4–8 mg daily), a significant increase in the hypotensive effect of the latter was observed. This effect lasts up to
12 hours and may manifest itself in individual symptoms, including dizziness. This combination of drugs is not recommended for use (see section "Special instructions").

Clinical pharmacodynamic studies have examined the potential of tadalafil to enhance the hypotensive effects of antihypertensive drugs. The main classes of drugs studied were: calcium channel blockers (amlodipine), angiotensin-converting enzyme inhibitors (enalapril), β-adrenoceptor blockers (metoprolol), thiazide diuretics (bendrofluazide), and angiotensin II receptor blockers (various types and doses, alone and in combination with thiazide diuretics, calcium channel blockers, β-adrenoceptor blockers, and/or α-adrenoceptor blockers). Tadalafil (10 mg, except for interaction studies with angiotensin II receptor blockers and amlodipine, where the effect of a 20 mg dose was studied) did not show significant interactions with the above-mentioned classes of drugs. Another clinical pharmacology study investigated the concomitant use of tadalafil (20 mg) with multiple antihypertensive agents (up to four). In patients taking multiple antihypertensive agents, changes in blood pressure were dependent on the level of blood pressure control. Thus, in patients with well-controlled hypertension, the reduction in blood pressure was small and consistent with that in healthy volunteers. In patients with uncontrolled hypertension, the reduction in blood pressure was greater, although in most patients this reduction in blood pressure was not accompanied by hypotensive symptoms. In patients receiving concomitant antihypertensive agents, the use of tadalafil at a dose of 20 mg may lead to a decrease in blood pressure, which (except in the case of concomitant use with α-adrenoceptor blockers) is generally small and clinically insignificant. Analysis of data from the third phase of the clinical trial did not reveal any differences in adverse reactions occurring in patients treated with tadalafil with concomitant antihypertensive agents and those treated with tadalafil alone. Nevertheless, appropriate advice should be given regarding the possible lowering of blood pressure in patients treated with antihypertensive drugs and Pinap.

Riociguat.

In preclinical studies, an additive hypotensive effect was observed when PDE5 inhibitors were co-administered with riociguat. In clinical studies, riociguat was shown to potentiate the hypotensive effect of PDE5 inhibitors. There was no evidence of a beneficial clinical effect of this combination in the study population. The concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated (see section 4.3).

5-α-reductase inhibitors.

In a clinical trial comparing tadalafil 5 mg and finasteride 5 mg to placebo and finasteride 5 mg for the treatment of symptoms of benign prostatic hyperplasia, no new adverse reactions were identified. However, since drug-drug interaction studies to evaluate the effects of tadalafil and 5-α-reductase inhibitors have not been conducted, caution should be exercised when prescribing tadalafil to patients receiving 5-α-reductase inhibitors.

CYP1A2 substrates (e.g. theophylline).

In a clinical pharmacology study, no pharmacokinetic interaction was observed when tadalafil (10 mg) was coadministered with theophylline (a non-selective phosphodiesterase inhibitor). The only pharmacodynamic effect was a slight increase in heart rate (3.5 beats/min). The possibility of this effect occurring with the concomitant use of tadalafil and theophylline should be considered, although it is minor and of no clinical significance.

Ethinylestradiol and terbutaline.

Tadalafil increased the bioavailability of oral ethinylestradiol formulations. This increase in bioavailability may be expected when co-administered with terbutaline (oral), although the clinical consequences of this combination are unknown.

Alcohol.

Alcohol (mean maximum concentration 0.08%) had no effect on the concomitant use of tadalafil (at a dose of 10 or 20 mg). There were also no changes in tadalafil concentrations during the next 3 hours after the simultaneous intake of alcohol with tadalafil. Alcohol was administered in such a way as to achieve the maximum level of alcohol absorption (administration on an empty stomach after an overnight fast and without food for 2 hours after alcohol administration). Tadalafil (at a dose of 20 mg) did not lead to a statistically significant decrease in mean blood pressure values against the background of alcohol intake (0.7 g/kg or approximately 180 ml of 40% alcohol (vodka) in a man with a body weight
80 kg), but some patients experienced postural dizziness and orthostatic hypotension. Tadalafil administration with lower doses of alcohol (0.6 g/kg) did not cause hypotension, and dizziness was observed with the same frequency as with alcohol alone. The effect of alcohol on cognitive function was not enhanced by concomitant use of tadalafil (10 mg).

Drugs metabolized by cytochrome P-450.

Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolized by CYP450 isoforms. In clinical studies, tadalafil has been shown not to inhibit or induce CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9, and CYP2C19.

Tadalafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC)
S-warfarin or R-warfarin (CYP2C9 substrates), and had no effect on warfarin-induced prothrombin time.

Aspirin.

Tadalafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetylsalicylic acid.

Antidiabetic drugs.

Specific studies of the interaction of tadalafil with antidiabetic drugs have not been conducted.

Application features

Before starting treatment with Pinap.

Before using the drug, the doctor should collect a medical history and conduct a physical examination of the patient, identify potential root causes of erectile dysfunction and benign prostatic hyperplasia, and prescribe an appropriate course of treatment.

Before initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status of their patients, as there is a degree of cardiac risk associated with sexual activity. Tadalafil has a vasodilatory effect, which may lead to a slight and transient decrease in blood pressure (see section 5.1) and potentiate the hypotensive effect of nitrates (see section 4.3).

Before starting tadalafil therapy for symptoms of benign prostatic hyperplasia, the patient should be examined to exclude possible prostate carcinoma and the cardiovascular system should be carefully assessed (see section "Contraindications").

Evaluation of erectile dysfunction should include identification of the potential underlying cause and appropriate treatment after appropriate medical evaluation. It is unknown whether Pinap is effective in patients who have undergone pelvic surgery or radical prostatectomy without nerve sparing.

Cardiovascular system.

Serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina, ventricular arrhythmia, cerebrovascular accident, transient ischemic attack, chest pain, palpitations, and tachycardia, have been reported in the postmarketing setting and/or in clinical trials. The majority of patients who experienced these adverse reactions had a history of cardiovascular risk factors. However, it is currently not possible to determine with certainty whether these events are related to the risk factors, the use of Pinapu, the sexual activity of the patients, or a combination of these or other factors.

In patients receiving concomitant antihypertensive therapy, tadalafil may potentiate the decrease in blood pressure. If daily therapy with Pinap is initiated, the clinical need for dose adjustment of antihypertensive therapy should be considered.

Pinap should be prescribed with caution to patients taking α1-blockers, as in some patients the simultaneous use of these drugs may lead to symptomatic hypotension (see section "Interaction with other medicinal products and other types of interactions"). The combined use of tadalafil and doxazosin is not recommended.

Organs of vision.

Cases of visual impairment and non-arteritic anterior ischemic optic neuropathy (NAPION) have been reported with the use of Pinapu and other PDE5 inhibitors. Analysis of observational data has shown an increased risk of developing acute non-arteritic anterior ischemic optic neuropathy (NAPION) in men with erectile dysfunction after the use of tadalafil or other PDE5 inhibitors. Since this increased risk is possible in all patients taking tadalafil, the physician should warn the patient about the need to immediately stop taking tadalafil and seek medical help in case of sudden vision loss (see section "Contraindications").

Deterioration or sudden loss of hearing.

Cases of sudden hearing loss have been reported following the use of tadalafil. Regardless of the presence of other risk factors (such as age, diabetes, hypertension, and history of hearing loss), patients should be advised to discontinue tadalafil and seek medical attention in the event of sudden hearing loss or deterioration.

Renal and hepatic failure.

Daily use of Pinap is not recommended in patients with severe renal impairment due to increased exposure (AUC) to tadalafil, limited clinical experience, and poor ability to influence its clearance by dialysis.

Clinical data on the use of Pinapu for daily use in patients with severe hepatic impairment (Child-Pugh class C) are limited.

Daily use of the drug for both erectile dysfunction and benign prostatic hyperplasia has not been evaluated in patients with hepatic impairment. Before prescribing Pinap, the physician should carefully assess the individual benefits/risks of therapy.

Priapism and anatomical deformation of the penis.

Pinap should be prescribed with caution to patients with anatomical deformities of the penis (such as angular curvature, cavernous fibrosis, or Peyronie's disease) or to patients who have conditions that may contribute to priapism (such as sickle cell anemia, myeloma, or leukemia).

Concomitant use with CYP3A4 inhibitors.

Pinap should be prescribed with caution to patients taking CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), since when used together with tadalafil, an increase in tadalafil exposure (AUC) is observed.
(see section “Interaction with other medicinal products and other types of interactions”).

Concomitant use with other drugs for the treatment of erectile dysfunction.

The safety and efficacy of Pinap in combination with other PDE5 inhibitors or other agents for the treatment of erectile dysfunction have not been studied, therefore patients should be informed that Pinap should not be taken in such combinations.

Lactose.

The drug contains lactose monohydrate, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use the drug.

Use during pregnancy or breastfeeding

Pinup is not indicated for use by women.

Pregnancy. There are limited data from the use of tadalafil in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of Pinapu during pregnancy.

Breastfeeding. Available pharmacodynamic/toxicological data in animals indicate excretion of tadalafil in milk. A risk to the breastfed infant cannot be excluded. Pinap should not be used during breast-feeding.

Fertility: Effects that may indicate impaired fertility have been observed in dogs. In two clinical studies, it was determined that such an effect is not expected in humans, although a decrease in sperm concentration was observed in some males (see section 5.1).

Ability to influence reaction speed when driving vehicles or other mechanisms

Pinapu has little effect on the ability to drive and use machines. Although the frequency of reports of dizziness in clinical trials with placebo and in clinical trials with tadalafil was similar, patients should be aware of how Pinapu affects them before driving or operating machinery.

Method of administration and doses

For oral use.

Erectile dysfunction in adult men.

The recommended dose is 10 mg before anticipated sexual activity, regardless of food intake. Patients in whom tadalafil 10 mg does not produce an adequate effect may be given a 20 mg dose.

The drug can be taken 30 minutes before sexual activity.

The maximum recommended frequency of administration is once a day.

Tadalafil 10 mg and 20 mg are intended for use before anticipated sexual activity and are not recommended for daily use.

If frequent use of Pinapu is anticipated (at least twice a week), a regimen of daily use of lower doses of Pinapu may be more appropriate, based on patient choice and physician judgment. For such patients, the recommended dose is
5 mg/day at approximately the same time. The dose may be reduced to 2.5 mg/day based on individual tolerance. The appropriateness of continued daily use should be reassessed periodically.

Benign prostatic hyperplasia in adult men.

For daily use, the recommended dose is 5 mg/day at approximately the same time each day, without regard to meals. For the treatment of adult men with erectile dysfunction and symptoms of benign prostatic hyperplasia, the recommended dose for daily use is 5 mg/day at approximately the same time each day. For patients who cannot tolerate tadalafil 5 mg/day for the treatment of benign prostatic hyperplasia, alternative therapy should be considered, as the efficacy of tadalafil 2.5 mg/day for the treatment of benign prostatic hyperplasia has not been evaluated.

Special patient populations.

Elderly men: No dose adjustment is required.

Men who have kidney failure.