Instructions for Maxigra Drive film-coated tablets 20 mg No. 2
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, microcrystalline cellulose, povidone K 30, poloxamer, sodium lauryl sulfate, croscarmellose sodium, colloidal anhydrous silicon dioxide, magnesium stearate;
tablet coating for 2.5 mg: polyvinyl alcohol, titanium dioxide (E 171), macrogol, talc;
Tablet coating 5 mg, 10 mg and 20 mg: polyvinyl alcohol, titanium dioxide (E 171), macrogol, talc, iron oxide yellow (E 172), iron oxide red (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties:
2.5 mg: film-coated tablets, white or almost white, round, biconvex, 4.9–5.3 mm in diameter;
5 mg: film-coated tablets, light brown, oblong, biconvex, 7.9–8.3 mm long, 3.9–4.3 mm wide;
10 mg: film-coated tablets, light orange, oblong, biconvex, with a break line on one side, length 10.9–11.4 mm, width 5.4–5.9 mm;
20 mg: film-coated tablets, light pink, oblong, biconvex, with a score on one side, 14.9–15.4 mm long, 7.1–7.6 mm wide. After breaking, the tablet core is white or almost white.
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 penile tissues, resulting in an erection. Tadalafil does not exert 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's effect on 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 muscle 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 PDE 5 over PDE 3 is important because PDE 3 is an enzyme that plays a role in the contraction of the heart muscle. In addition, tadalafil is approximately 700 times more potent for PDE 5 than for PDE 6, an enzyme found in the retina and responsible for phototransduction. Tadalafil is also 10,000 times more potent for PDE 5 than for 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). The obtained clinical study data confirm the low affinity of tadalafil for PDE 6 compared to PDE 5. In all clinical studies, changes in color perception were rarely (< 0.1%).
Three clinical studies were conducted in men to evaluate the potential effects of tadalafil 10 mg (one study of 6 months duration) and 20 mg (one study of 6 months and one of 9 months duration) on spermatogenesis when administered once daily. Two of the three studies showed clinically insignificant decreases in sperm count and concentration associated with tadalafil. These effects were not associated with changes in other characteristics such as sperm motility, morphology, and blood follicle-stimulating hormone levels.
Three clinical studies were conducted in 1054 patients to determine the time to onset of effect of tadalafil, which demonstrated a statistically significant improvement in erectile function, as well as efficacy for 36 hours and the detection of the effect as early as 16 minutes after dosing compared to placebo (tadalafil taken as needed).
In a 12-week study of 186 patients (142 patients on tadalafil, 44 patients on placebo) with erectile dysfunction secondary to spinal cord injury, tadalafil showed significant improvement in erectile function, with an average success rate of 48% for tadalafil 10 mg or 20 mg (dose titrated, as needed) compared with 17% for placebo.
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 tadalafil 5 mg and 50% for tadalafil 2.5 mg compared to 31% and 37% for placebo. In the trials in patients with erectile dysfunction secondary to diabetes, the average success rate was 41% and 46% for tadalafil 5 mg and 2.5 mg, respectively, compared to 28% for placebo. 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 were treated with tadalafil 5 mg once daily and placebo. The average success rate was 68% in the tadalafil group compared with 52% in the placebo group.
Benign prostatic hyperplasia.
Tadalafil has been studied in four 12-week clinical trials in 1500 patients with symptoms of benign prostatic hyperplasia. In these clinical trials, tadalafil 5 mg demonstrated improvements in the International Prostatic Symptom Score (IPSS) compared to placebo (IPSS improvement scores for tadalafil 5 mg were -4.8, -5.6, -6.1 and -6.3, compared to -2.2, -3.6, -3.8, -4.2 for placebo). Improvements in the International Prostatic Symptom Score (IPSS) were observed after as little as 1 week of treatment. In one clinical trial, where tamsulosin 0.4 mg was also included as an active comparator, the MSPS improvement scores for tadalafil 5 mg, tamsulosin, and placebo were –6.3, –5.7, and –4.2, respectively.
One of these studies assessed both improvement in erectile function and relief of symptoms of benign prostatic hyperplasia in patients with both conditions. Improvement in erectile function on the International Erectile Function Index and the International Prostatic Symptom Score were 6.5 and -6.1 with tadalafil 5 mg compared with 1.8 and -3.8 with placebo, respectively. The average rate of successful sexual intercourse attempts per subject in the study was 71.9% in the tadalafil 5 mg group and 48.3% in the placebo group.
The maintenance of the achieved effect of tadalafil was assessed in an additional open-label study, which found that the improvement in the total international prostatic symptom score observed over 12 weeks was maintained for up to 1 additional year after treatment with tadalafil 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.
The rate and extent of absorption of tadalafil are independent of food intake, so tadalafil 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.
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 renal impairment.
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 volunteers. 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 from 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, resulting in a 25% increase in 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 is negligible.
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 tadalafil in patients with severe hepatic impairment (Child-Pugh Class C). There are no data on the use of tadalafil once daily in patients with hepatic impairment. The physician should carefully assess the individual benefits/risks of prescribing tadalafil once daily.
Diabetic patients: 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 a dosage of 2.5 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 symptoms of benign prostatic hyperplasia in adult men. Treatment of erectile dysfunction in adult men. The drug is effective for the treatment of erectile dysfunction in the presence of sexual stimulation.
For a dosage of 10 mg. Treatment of erectile dysfunction in adult men. The drug is effective for the treatment of erectile dysfunction in the presence of sexual stimulation.
For a dosage of 20 mg. Treatment of erectile dysfunction in adult men. The drug is effective for the treatment of erectile dysfunction in the presence of sexual stimulation
Tadalafil is not indicated for use in 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).
Tadalafil 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 uncontrolled arrhythmias, arterial hypotension (<90/50 mm Hg) or uncontrolled hypertension;
patients after a stroke that occurred within the last 6 months.
Tadalafil is contraindicated in patients with loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy (NAPION), whether or not this was related to previous exposure to PDE5 inhibitors (see section 4.4).
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 conducted at 10 mg and 20 mg doses, the results of which are presented below. In interaction studies using only 10 mg tadalafil, 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 increase (see section 4.8).
Transporters.
The effect of transporters, such as p-glycoprotein, on the distribution of tadalafil is unknown. Therefore, 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 tadalafil 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 did not manifest itself after 48 hours after the last dose of tadalafil. Therefore, if the use of nitrates is medically necessary in a life-threatening condition for a patient who is prescribed tadalafil at any dose (2.5-20 mg), then at least 48 hours should elapse after the last dose of tadalafil before using nitrates. 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).
When tadalafil (5 mg once daily or 20 mg as a single dose) was co-administered with the α-adrenergic 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 be manifested by individual symptoms, including dizziness. This combination of drugs is not recommended for use (see section "Special warnings and precautions for use").
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 the interaction studies with angiotensin II receptor blockers and amlodipine, where the effect of the 20 mg dose was studied) did not show any significant interaction 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 receiving 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 a phase III clinical trial did not reveal any differences in adverse reactions occurring in patients treated with tadalafil with concomitant antihypertensive agents compared to those treated with tadalafil alone. Nevertheless, appropriate advice should be given regarding the potential for blood pressure lowering in patients treated with antihypertensive agents and tadalafil.
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 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 in the presence of alcohol (0.7 g/kg or approximately 180 ml of 40% alcohol (vodka) in a man weighing 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 the exposure (AUC) of 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 Maxigra Drive.
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 tadalafil 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 clear whether these events are related to the risk factors, tadalafil use, the sexual activity of the patients, or a combination of these or other factors.
In patients receiving concomitant antihypertensive therapy, tadalafil may potentiate the reduction in blood pressure. If daily tadalafil therapy is initiated, the clinical need for dose adjustment of antihypertensive therapy should be considered.
Caution should be exercised when prescribing tadalafil to patients taking α1-blockers, as concomitant administration of these drugs may lead to symptomatic hypotension in some patients (see section 4.5). The combined use of tadalafil and doxazosin is not recommended.
Organs of vision.
Cases of visual impairment and NAPION have been reported with the use of tadalafil and other PDE5 inhibitors. Analysis of observational data has shown an increased risk of developing acute 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 loss of vision (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 Maxigra Drive 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 tadalafil 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 tadalafil, the physician should carefully assess the individual benefit/risk of therapy.
Priapism and anatomical deformation of the penis.
Tadalafil should be prescribed with caution in patients with anatomical deformities of the penis (such as angular curvature, cavernous fibrosis or Peyronie's disease) or in patients who have conditions that may predispose to priapism (such as sickle cell anemia, myeloma or leukemia).
Concomitant use with CYP3A4 inhibitors.
Caution should be exercised when prescribing tadalafil to patients taking CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin) as co-administration with tadalafil has been associated with an increase in tadalafil exposure (AUC) (see section 4.5).
Concomitant use with other drugs for the treatment of erectile dysfunction.
The safety and efficacy of tadalafil 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 tadalafil should not be taken in such combinations.
Lactose.
The drug contains lactose monohydrate. Maxigra Drive should not be prescribed to patients with rare hereditary forms of galactose intolerance, glucose-galactose malabsorption syndrome and Lapp lactase deficiency.
Use during pregnancy or breastfeeding
Maxigra Drive is not indicated for use in 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 tadalafil during pregnancy.
Breastfeeding. Available pharmacodynamic/toxicological data in animals indicate excretion of tadalafil in milk. A risk to the breastfed infant cannot be excluded. Maxigra Drive 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). In clinical studies, it was determined that impaired fertility is not expected in humans, although a decrease in sperm concentration was observed in some males.
Ability to influence reaction speed when driving vehicles or other mechanisms
Tadalafil has negligible influence 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 Maxigra Drive 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 tadalafil is anticipated (at least twice a week), a daily regimen of lower doses of tadalafil may be more appropriate, based on patient preference and physician judgment. For such patients, the recommended dose is 5 mg/day taken at approximately the same time each day. 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
