Ciatuf

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CIATUFF (CIATUFF)

Composition:

Active substance: tadalafil;

1 tablet contains 10 mg or 20 mg of tadalafil;

Excipients: copovidone; polyethylene glycol glyceryl monostearate; lactose monohydrate; colloidal anhydrous silicon dioxide; microcrystalline cellulose; sodium croscarmellose; magnesium stearate;

Coating of 10 mg tablet: Opadry Yellow 03K82779 (hypromellose, titanium dioxide (E 171), triacetin, talc, yellow iron oxide (E 172)), purified water;

Coating of 20 mg tablet: Opadry Yellow 03K82780 (hypromellose, titanium dioxide (E 171), triacetin, talc, yellow iron oxide (E 172)), purified water.

Dosage form. Film-coated tablets.

Main physicochemical properties:

10 mg tablets: film-coated tablets, light yellow in color, oval-shaped, with the imprint "10" on one side and "TL" on the other;

20 mg tablets: film-coated tablets, yellow in color, oval-shaped, with the imprint "20" on one side and "TL" on the other.

Pharmacotherapeutic group.

Agents for the treatment of erectile dysfunction. Tadalafil. ATC code G04BE08.

Pharmacological Properties

Pharmacodynamics

Mechanism of action

Tadalafil is a selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). When sexual stimulation causes local release of nitric oxide, inhibition of PDE5 by tadalafil results in increased levels of cGMP in the corpus cavernosum. This leads to relaxation of smooth muscles and increased blood flow into penile tissues, thereby producing an erection. Tadalafil does not exert its effect in the treatment of erectile dysfunction in the absence of sexual stimulation.

The inhibitory effect on cGMP concentration in the corpus cavernosum is also observed in smooth muscles of the prostate, bladder, and their blood vessels supplying these organs. The resulting vascular relaxation increases blood perfusion and may contribute to the reduction of symptoms of benign prostatic hyperplasia. These vascular effects may be complemented by inhibition of afferent nerve activity in the bladder and relaxation of 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 the smooth muscles of the corpus cavernosum, vascular and visceral smooth muscles, skeletal muscles, platelets, kidneys, lungs, and cerebellum. The effect of tadalafil on PDE5 is stronger than on other phosphodiesterases. The activity of tadalafil against PDE5 is 10,000 times greater than its effect on PDE1, PDE2, PDE4, and PDE7, which are present in the heart, brain, blood vessels, liver, leukocytes, skeletal muscles, and other organs. Tadalafil is 10,000 times more potent against PDE5 than against PDE3, an enzyme present in the heart and blood vessels. This selectivity for PDE5 over PDE3 is important because PDE3 plays a role in myocardial contraction. In addition, tadalafil is approximately 700 times more potent against PDE5 than against PDE6, an enzyme present in the retina and responsible for phototransduction. Tadalafil is also 10,000 times more potent against PDE5 than against PDE7, PDE8, PDE9, and PDE10.

Clinical efficacy and safety

In healthy volunteers, tadalafil showed no clinically significant differences compared to placebo in systolic and diastolic blood pressure in the supine position (mean maximum decrease of 1.6/0.8 mm Hg, respectively), systolic and diastolic blood pressure in the standing position (mean maximum decrease of 0.2/4.6 mm Hg, respectively), or significant changes in heart rate.

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

Three clinical studies were conducted in men to evaluate the potential effect of tadalafil on spermatogenesis at doses of 10 mg (one 6-month study) and 20 mg (one 6-month and one 9-month study), administered once daily. In two of the three studies, a clinically insignificant decrease in sperm count and concentration associated with tadalafil use was observed. These effects were not related to changes in other parameters such as sperm motility, morphology, or serum follicle-stimulating hormone levels.

Erectile dysfunction

Three clinical studies involving 1054 patients were conducted to determine the onset of tadalafil's effect, demonstrating statistically significant improvement in erectile function, efficacy lasting up to 36 hours, and an effect observed as early as 16 minutes after dosing compared to placebo (on-demand tadalafil use).

In a 12-week study involving 186 patients (142 receiving tadalafil, 44 receiving placebo) with erectile dysfunction secondary to spinal cord injury, tadalafil significantly improved erectile function, with the mean success rate of attempts with tadalafil 10 mg or 20 mg (dose titration, on-demand use) being 48% compared to 17% in the placebo group.

Tadalafil at doses ranging from 2 mg to 100 mg was evaluated in 16 clinical studies involving 3250 patients, including patients with erectile dysfunction of varying severity (mild, moderate, severe), of different etiologies, age groups (21 to 86 years), and ethnic backgrounds. In most patients, erectile dysfunction had been present for at least one year. In primary efficacy studies, the improvement rate was 81% in the tadalafil group compared to 35% in the placebo group. Additionally, patients with erectile dysfunction of varying severity reported improvement during tadalafil treatment (success rates of 86%, 83%, and 72% in patients with mild, moderate, and severe erectile dysfunction, respectively, compared to 45%, 42%, and 19% in the placebo group). In primary efficacy studies, the success rate was 75% in the tadalafil group compared to 32% in the placebo group.

In a 12-week study involving 186 patients (142 receiving tadalafil, 44 receiving placebo) with erectile dysfunction secondary to spinal cord injury, tadalafil significantly improved erectile function, with the mean success rate of attempts with tadalafil 10 mg or 20 mg (dose titration, on-demand use) being 48% compared to 17% in the placebo group.

Children

One study was conducted in children with Duchenne muscular dystrophy (DMD), in which no confirmed evidence of efficacy was demonstrated. This study of tadalafil efficacy was a randomized, double-blind, placebo-controlled, three-arm study involving 331 male children aged 7 to 14 years with DMD who were concurrently receiving 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, measured by the change in distance in the 6-minute walk test. The least squares mean change in 6-minute walk test 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). Confirmed efficacy was also not demonstrated in subsequent analyses of this study. Overall safety results from this study were generally consistent with the known safety profile of tadalafil and adverse events expected in the pediatric DMD population receiving corticosteroid therapy.

Pharmacokinetics

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

The rate and extent of tadalafil absorption are not affected by food intake; therefore, Siatuf can be taken regardless of meals. The time of dosing (morning or evening) had no clinically significant effect on the rate and extent of absorption.

Distribution. The mean volume of distribution is approximately 63 L, indicating that tadalafil is distributed into tissues. At therapeutic concentrations, 94% of tadalafil in plasma is protein-bound. Protein binding is not affected by impaired renal function.

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

Metabolism. Tadalafil is primarily metabolized by cytochrome P450 isoform 3A4 (CYP3A4). The major circulating metabolite is methylcatechol glucuronide. This metabolite has PDE5 inhibitory activity 13,000 times lower than that of tadalafil. Therefore, the metabolite is not expected to have clinical activity at observed concentrations.

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

Linearity/Non-linearity of pharmacokinetics. The pharmacokinetics of tadalafil in healthy volunteers are linear over time and dose. Within the dose range of 2.5 mg to 20 mg, the area under the concentration-time curve (AUC) increases proportionally with dose. Steady-state plasma concentrations are achieved within 5 days with once-daily dosing.

The pharmacokinetics of the medicinal product are similar in patients with and without erectile dysfunction.

Special patient groups

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

Renal impairment. In clinical pharmacology studies using single doses of tadalafil (5–20 mg), the AUC of tadalafil was nearly doubled in patients with mild (creatinine clearance 51–80 mL/min) or moderate (creatinine clearance 31–50 mL/min) renal impairment, as well as in patients with end-stage renal disease on dialysis. In patients undergoing hemodialysis, Cmax was 41% higher than in healthy volunteers. The effect of hemodialysis on tadalafil elimination is negligible.

Hepatic impairment. Exposure to tadalafil (AUC) in patients with mild to moderate hepatic impairment (Child-Pugh classes A and B) is comparable to that in healthy volunteers when a 10 mg dose is administered. Safety data for tadalafil use in patients with severe hepatic impairment (Child-Pugh class C) are limited. There are no data on the use of tadalafil at doses above 10 mg in patients with hepatic impairment. The physician should carefully assess the individual benefit/risk ratio for using Siatuf.

Patients with diabetes mellitus. The AUC of tadalafil in patients with diabetes mellitus was approximately 19% lower than in healthy volunteers. This difference in exposure does not require dose adjustment.

Clinical characteristics.

Indications.

Treatment of erectile dysfunction in adult men. The drug is effective in the presence of sexual stimulation.

Ciafu is not indicated for use in women.

Contraindications.

Hypersensitivity to tadalafil or to any other component of the drug.

During clinical studies, tadalafil demonstrated the ability to potentiate the hypotensive effect of nitrates. This is considered to be a consequence of the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway. Therefore, the use of tadalafil is contraindicated in patients taking organic nitrates in any dosage form (see section "Interaction with other medicinal products and other types of interactions").

Ciafu should not be used in men with cardiovascular diseases for whom sexual activity is inadvisable. Physicians should consider the potential cardiovascular risk associated with sexual activity in patients with a history of cardiovascular disease.

The following groups of patients with cardiovascular disorders were not included in clinical trials; therefore, tadalafil use is contraindicated in these patients:

• Patients who have had myocardial infarction within the last 90 days;
• Patients with unstable angina or angina occurring during sexual intercourse;
• Patients with heart failure classified as class 2 or higher according to the New York Heart Association classification within the last 6 months;
• Patients with uncontrolled arrhythmias, arterial hypotension (< 90/50 mm Hg), or uncontrolled hypertension;
• Patients who have had a stroke within the last 6 months.

Ciafu is contraindicated in patients with loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether it was associated with previous use of PDE5 inhibitors or not (see section "Special precautions").

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 "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Interaction studies were conducted at doses of 10 mg and 20 mg; data are provided below. Regarding interaction studies in which only tadalafil 10 mg was used, clinically significant interactions with higher doses cannot be excluded.

Effect of other medicinal products on tadalafil

Cytochrome CYP450 inhibitors

Tadalafil is primarily metabolized by CYP3A4. The selective CYP3A4 inhibitor ketoconazole (200 mg daily) increases the AUC of tadalafil (10 mg) by 2-fold and Cmax by 15% compared to tadalafil alone. Ketoconazole (400 mg daily) increases the 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, increases the 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 used with caution, as they are expected to increase plasma concentrations of tadalafil when used concomitantly (see section "Special precautions"). This may consequently increase the frequency of adverse reactions (see section "Adverse reactions").

Transporters

The effect of transporters, such as P-glycoprotein, on tadalafil distribution is unknown. Therefore, there is a potential for drug interactions mediated by transporter inhibition.

Cytochrome CYP450 inducers

The CYP3A4 inducer rifampicin reduces tadalafil AUC by 88% compared to tadalafil alone (10 mg). This reduction in concentration may lead to decreased efficacy of tadalafil; the extent of efficacy reduction is unknown. Concomitant use of other CYP3A4 inducers such as phenobarbital, phenytoin, and carbamazepine may also reduce tadalafil plasma concentrations.

Effect of tadalafil on other medicinal products

Nitrates. During clinical studies, tadalafil (5 mg, 10 mg, 20 mg) demonstrated the ability to potentiate the hypotensive effects of nitrates. Therefore, the use of Ciafu in patients receiving treatment with organic nitrates in any form is contraindicated (see section "Contraindications"). Based on a clinical study involving 150 patients who received tadalafil 20 mg daily for 7 days and sublingual nitroglycerin 0.4 mg (at varying time intervals), this interaction lasted more than 24 hours and was not observed after 48 hours following the last dose of tadalafil. Therefore, if nitrates are medically necessary for a patient receiving Ciafu at any dose (2.5–20 mg), at least 48 hours must elapse after the last dose of Ciafu before administering nitrates. In such cases, nitrate administration should be performed under close medical supervision with appropriate hemodynamic monitoring.

Antihypertensive agents (including calcium channel blockers)

Significant potentiation of the hypotensive effect of the α-adrenoreceptor blocker doxazosin (4–8 mg daily) was observed during concomitant use with tadalafil (5 mg once daily or a single 20 mg dose). This effect lasts up to 12 hours and may manifest as individual symptoms, including dizziness. This combination is not recommended for use (see section "Special precautions").

In interaction studies involving a limited number of healthy volunteers, the above effects were not reported with concomitant use of alfuzosin or tamsulosin. Tadalafil should be prescribed with caution to patients receiving treatment with any α-adrenoreceptor blockers, especially elderly individuals. Treatment should be initiated at the lowest dose and gradually increased.

In clinical pharmacodynamic studies, the potential of tadalafil to enhance the hypotensive effects of antihypertensive agents was evaluated. Major drug classes were studied: calcium channel blockers (amlodipine), angiotensin-converting enzyme inhibitors (enalapril), β-blockers (metoprolol), thiazide diuretics (bendroflumethiazide), and angiotensin II receptor blockers (various types and doses, alone or in combination with thiazide diuretics, calcium channel blockers, β-blockers, and/or α-adrenoreceptor blockers). Tadalafil (10 mg dose, except for interaction studies with angiotensin II receptor blockers and amlodipine, where the 20 mg dose was studied) did not show significant interaction with the above-mentioned drug classes. In another clinical pharmacology study, concomitant use of tadalafil (20 mg) with multiple antihypertensive agents (up to four) was investigated. In patients taking multiple antihypertensive drugs, blood pressure changes depended on the level of blood pressure control. Thus, in patients with well-controlled hypertension, blood pressure reduction was minimal and comparable to that in healthy volunteers. In patients with uncontrolled hypertension, blood pressure reduction was greater, although in most patients this reduction did not cause hypotensive symptoms. In patients receiving concomitant antihypertensive therapy, tadalafil 20 mg may cause blood pressure reduction, which (except in combination with α-adrenoreceptor blockers) is generally minimal and clinically insignificant. Analysis of phase III clinical trial data did not reveal differences in adverse reactions between patients treated with tadalafil with concomitant antihypertensive therapy and those treated with tadalafil alone. Nevertheless, appropriate advice regarding possible blood pressure reduction should be provided to patients taking antihypertensive drugs and Ciafu.

Riociguat

Preclinical studies revealed an additive hypotensive effect when PDE5 inhibitors were used concomitantly with riociguat. Clinical studies showed that riociguat potentiates the hypotensive effect of PDE5 inhibitors. There was no evidence of favorable clinical effect of this combination in the studied population. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated (see section "Contraindications").

5-α-reductase inhibitors

In a clinical study comparing concomitant use of tadalafil 5 mg and finasteride 5 mg versus placebo and finasteride 5 mg for relief of benign prostatic hyperplasia symptoms, no new adverse reactions were observed. However, since no drug interaction studies were conducted to evaluate the effects of tadalafil and 5-α-reductase inhibitors, tadalafil should be prescribed with caution to patients receiving treatment with 5-α-reductase inhibitors.

CYP1A2 substrates (e.g., theophylline)

In a clinical pharmacology study, no pharmacokinetic interaction was observed when tadalafil (10 mg) was administered 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 should be considered when tadalafil and theophylline are used concomitantly, despite its minimal and clinically insignificant nature.

Ethinylestradiol and terbutaline

Tadalafil increased the bioavailability of oral formulations containing ethinylestradiol. Such an increase in bioavailability may be expected when used concomitantly with terbutaline (orally), although the clinical consequences of this combination are unknown.

Alcohol

Alcohol (mean maximum concentration 0.08%) did not affect the concomitant use of tadalafil (10 or 20 mg). No changes in tadalafil concentration were observed during the following three hours after simultaneous intake of alcohol and tadalafil. Alcohol was administered to achieve maximum alcohol absorption (on an empty stomach after overnight fasting and without food for 2 hours after alcohol intake). Administration of tadalafil (20 mg) did not result in statistically significant reduction in mean blood pressure when combined with alcohol (0.7 g/kg or approximately 180 ml of 40% alcohol (vodka) in an 80 kg man), although postural dizziness and orthostatic hypotension were observed in some patients. Administration of tadalafil with lower alcohol doses (0.6 g/kg) did not cause hypotension, and dizziness occurred at the same frequency as with alcohol alone. The effect of alcohol on cognitive function was not enhanced when tadalafil (10 mg) was used concomitantly.

MEDICINAL PRODUCTS METABOLIZED BY CYTOCHROME P450

Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal products metabolized by CYP450 isoenzymes. Clinical studies have demonstrated that tadalafil does not inhibit or induce CYP450 isoenzymes, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9, and CYP2C19.

CYP2C9 substrates (e.g., R-warfarin)

Tadalafil (10 mg and 20 mg) did not show clinically significant effects on the AUC of S-warfarin or R-warfarin (CYP2C9 substrates) and had no effect on warfarin-induced prothrombin time.

Acetylsalicylic acid

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

Antidiabetic medicinal products

Specific interaction studies between tadalafil and antidiabetic medicinal products have not been conducted.

Special precautions for use.

Before initiating treatment with Ciataf

Before using the medicinal product, the physician should determine the underlying causes of erectile dysfunction and prescribe an appropriate treatment course.

Prior to initiating any treatment for erectile dysfunction, physicians should carefully assess the cardiovascular status of their patients, as there is a certain degree of cardiovascular risk associated with sexual activity. Tadalafil exerts a vasodilatory effect, which may lead to a slight and transient decrease in blood pressure and may potentiate the hypotensive effect of nitrates.

It is unknown whether Ciataf is effective in patients who have undergone pelvic surgery or radical prostatectomy without nerve-sparing.

Cardiovascular system

During the post-marketing period and/or clinical trials, serious adverse reactions related to the cardiovascular system have been reported, including myocardial infarction, sudden cardiac death, unstable angina, ventricular arrhythmia, cerebrovascular disorders, transient ischemic attack, chest pain, palpitations, and tachycardia. Most patients who experienced such adverse reactions had pre-existing cardiovascular risk factors. However, it is currently not possible to definitively determine whether the aforementioned adverse reactions are related to these risk factors, the use of tadalafil, sexual activity, or a combination of these or other factors.

Ciataf should be prescribed with caution to patients taking α1-blockers, as in some individuals concomitant use of these medicinal products may lead to symptomatic hypotension (see section "Interaction with other medicinal products and other forms of interaction"). Combined use of tadalafil and doxazosin is not recommended.

Vision

Cases of visual disturbances, including central serous chorioretinopathy (CSCR) and non-arteritic anterior ischemic optic neuropathy (NAION), have been reported during the use of tadalafil and other PDE5 inhibitors. In most cases, symptoms of CSCR resolved spontaneously after discontinuation of tadalafil. Analysis of observational study data has shown an increased risk of acute NAION in men with erectile dysfunction following the use of tadalafil or other PDE5 inhibitors. Since this risk may be elevated in all patients using tadalafil, physicians should inform patients about the necessity to discontinue tadalafil and seek immediate medical attention in case of sudden vision loss, visual acuity disturbances, and/or visual distortion (see section "Contraindications").

Worsening or sudden hearing loss

Cases of sudden hearing loss following tadalafil administration have been reported. Regardless of the presence of other risk factors (age, diabetes, hypertension, or history of hearing loss), patients should be informed about the need to discontinue tadalafil and seek immediate medical attention in case of sudden hearing deterioration or hearing loss.

Hepatic impairment

Clinical safety data on a single dose of Ciataf in patients with severe hepatic impairment (Child-Pugh class C) are limited. When prescribing Ciataf to such patients, the physician should carefully evaluate the individual benefit-risk ratio of therapy.

Priapism and penile anatomical deformity

Patients experiencing an erection lasting 4 hours or longer should be advised to seek immediate medical attention. Without prompt treatment of priapism, damage to penile tissue and long-term loss of erectile function may occur.

Ciataf should be prescribed with caution to patients with anatomical penile deformity (e.g., angulation, cavernous fibrosis, or Peyronie’s disease) or conditions predisposing to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia).

Concomitant use with CYP3A4 inhibitors

Ciataf should be prescribed with caution to patients taking CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), as co-administration with tadalafil results in increased tadalafil AUC.

Concomitant use with other erectile dysfunction treatments

The safety and efficacy of Ciataf in combination with other PDE5 inhibitors or other medicinal products for the treatment of erectile dysfunction have not been studied; therefore, patients should not take Ciataf in such combinations.

Lactose

Ciataf contains lactose monohydrate and therefore should not be administered to patients with rare hereditary forms of galactose intolerance, glucose-galactose malabsorption, or lactase deficiency.

Sodium

One tablet of this medicinal product contains less than 1 mmol of sodium (23 mg), i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

Ciataf is not indicated for use in women.

Pregnancy. Data on the use of tadalafil in pregnant women are limited. Animal studies have not shown any direct or indirect harmful effects on pregnancy, embryonal/fetal development, parturition, or postnatal development. As a precautionary measure, it is advisable to avoid using Ciataf during pregnancy.

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

Fertility. Effects indicating impaired fertility were observed in dogs. In two clinical studies, fertility impairment was not expected in humans, although decreased sperm concentration was observed in some individuals (see section "Pharmacological properties").

Ability to influence reaction speed when driving or operating machinery.

The effect of Ciataf on the ability to drive or operate machinery is negligible. Although the frequency of dizziness reports during clinical trials with placebo and tadalafil was similar, patients should be aware of how this medicinal product affects them before driving or operating machinery.

Administration and Dosage

For oral use. Siatufu tablets should be taken with the recommended dose of active ingredient.

Adult Men

The recommended dose is 10 mg taken prior to anticipated sexual activity, regardless of food intake. For patients in whom 10 mg of tadalafil does not provide adequate effect, a dose of 20 mg may be used.

The medication should be taken at least 30 minutes before anticipated sexual activity.

The effectiveness of tadalafil lasts up to 36 hours after dosing.

The maximum recommended frequency of dosing is once per day.

Tadalafil 10 mg and 20 mg is intended for use prior to anticipated sexual activity and is not recommended for daily use.

If frequent use of Siatufu (at least twice weekly) is anticipated, a daily regimen with lower doses of Siatufu may be more appropriate, based on patient preference and physician decision. For such patients, the recommended dose is 5 mg once daily at approximately the same time each day. The dose may be reduced to 2.5 mg once daily based on individual tolerability. The need for long-term daily treatment should be periodically reassessed.

Special Patient Groups

Elderly Men. Dose adjustment is not required.

Men with Renal Impairment. Dose adjustment is not required in patients with mild or moderate renal impairment. For patients with severe renal impairment, the maximum recommended dose is 10 mg when using tablets of appropriate strength.

Men with Hepatic Impairment

The recommended dose of Siatufu is 10 mg prior to anticipated sexual activity, regardless of food intake.

Clinical safety data on the use of Siatufu in patients with severe hepatic impairment (Child-Pugh class C) are limited; if prescribed, the physician should carefully assess the individual benefit/risk ratio. There are no data on the use of Siatufu at doses above 10 mg in patients with hepatic impairment. There are no data on the use of the medication at doses of 2.5–5 mg once daily in patients with hepatic impairment; therefore, if prescribed, the physician should carefully assess the individual benefit/risk ratio when considering Siatufu at 2.5–5 mg once daily.

Men with Diabetes

Dose adjustment is not required.

Children

The medication is not intended for use in children.

Special Warnings on Disposal

Unused medication or waste material should be disposed of in accordance with current regulatory requirements.

Children.

The medication is not intended for use in children (under 18 years of age).

Overdose.

Symptoms. In healthy volunteers, single doses of tadalafil up to 500 mg and multiple daily doses up to 100 mg resulted in adverse reactions similar to those observed with lower doses of the drug.

Treatment. In case of overdose, standard symptomatic treatment should be applied as needed. Hemodialysis has minimal effect on tadalafil elimination.

Adverse reactions.

Summary of the medicinal product's safety profile

Adverse reactions most commonly observed during treatment for erectile dysfunction: headache, dyspepsia, back pain, myalgia, with frequency increasing with higher doses of tadalafil. Adverse reactions were short-term and mild to moderate in severity. Most cases of headache with daily administration of tadalafil at doses of 2.5 mg and 5 mg occurred within the first 10–30 days after initiation of treatment.

Tabulated data on adverse reactions

The table below contains data on adverse reactions from spontaneous reports and placebo-controlled clinical trials (overall included 8022 patients receiving tadalafil and 4422 patients receiving placebo) with on-demand use and daily use of tadalafil for treatment of erectile dysfunction, as well as daily use for treatment of benign prostatic hyperplasia.

Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), frequency not known (frequency cannot be estimated from the available data).

1 Most patients in whom such adverse reactions were observed had cardiovascular risk factors.

2 Adverse reactions reported during post-marketing surveillance and not observed in placebo-controlled clinical trials.

3 More frequently reported when tadalafil was used concomitantly with antihypertensive agents.

Individual adverse reactions. A slightly higher frequency of ECG abnormalities, most commonly sinus bradycardia, has been reported in patients receiving tadalafil once daily compared to those receiving placebo. Most of these ECG changes were not associated with clinical manifestations of adverse reactions.

Special patient groups. Clinical data on the use of tadalafil for the treatment of erectile dysfunction in patients aged 65 years and older are limited. During clinical trials of on-demand use of tadalafil for the treatment of erectile dysfunction, diarrhea was reported more frequently in patients aged 65 years and older.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 4 years.

Storage conditions.

Store at temperatures not exceeding 25 °C, in a place inaccessible to children. Protect from moisture.

Packaging.

2 tablets in a blister, 1 blister in a cardboard box; 4 tablets in a blister, 1 or 2 blisters in a cardboard box together with the instruction for medical use.

Prescription status.

Prescription only.

Manufacturer.

Aurobindo Pharma Limited – Unit VII.

Manufacturer's address and location of its operations.

Special Economic Zone, TSIIC, Plot No. S1, Sy. Nos. 411/P, 425/P, 434/P, 435/P and 458/P, Green Industrial Park, Polepally Village, Jedcherla Mandal, Mahabubnagar District, Telangana State, 509302, India.