In patients with BPH following single and multiple-doses of 20 mg tadalafil, no statistically significant differences in exposure (AUC and Cmax) were observed between elderly (70 to 85 years) and younger (≤60 years of age) subjects.
Animal studies showed vascular inflammation in tadalafil-treated mice, rats, and dogs.
The primary endpoint was time to cardiac ischemia. The mean difference in total exercise time was 3 seconds (tadalafil 10 mg minus placebo), which represented no clinically meaningful difference. Further statistical analysis demonstrated that tadalafil was non-inferior to placebo with respect to time to ischemia. Of note, in this study, in some subjects who received tadalafil followed by sublingual nitroglycerin in the post-exercise period, clinically significant reductions in blood pressure were observed, consistent with the augmentation by tadalafil of the blood-pressure-lowering effects of nitrates. Single oral doses of phosphodiesterase inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green), using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels.
This finding is consistent with the inhibition of PDE6, which is involved in photo transduction in the retina. In a study to assess the effects of a single dose of tadalafil 40 mg on vision (N=59), no effects were observed on visual acuity, intraocular pressure, or pupilometry. Across all clinical studies with CIALIS, reports of changes in color vision were rare (<0.1% of patients). Three studies were conducted in men to assess the potential effect on sperm characteristics of tadalafil 10 mg (one 6 month study) and 20 mg (one 6 month and one 9 month study) administered daily. There were no adverse effects on sperm morphology or sperm motility in any of the three studies.
In the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months, results showed a decrease in mean sperm concentrations relative to placebo, although these differences were not clinically meaningful. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. In addition there was no adverse effect on mean concentrations of reproductive hormones, testosterone, luteinizing hormone or follicle stimulating hormone with either 10 or 20 mg of tadalafil compared to placebo. The effect of a single 100-mg dose of tadalafil on the QT interval was evaluated at the time of peak tadalafil concentration in a randomized, double-blinded, placebo, and active (intravenous ibutilide) -controlled crossover study in 90 healthy males aged 18 to 53 years. The mean change in QT (Fridericia QT correction) for tadalafil, relative to placebo, was 3.5 milliseconds (two-sided 90% CI=1.9, 5.1). In mice and rats, lymphoid necrosis and hemorrhage were seen in the spleen, thymus, and mesenteric lymph nodes at unbound tadalafil exposure of 2- to 33-fold above the human exposure (AUCs) at the MRHD of 20 mg.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Cialis Generic | 20mg | 90 + 6 Pills | 154.71€ 147.34€ | |
| Cialis Super Active | 20mg | 20 + 4 Pills | 92.35€ 87.95€ | |
| Cialis Generic | 20mg | 20 Pills | 54.72€ 52.11€ | |
| Cialis Generic | 60mg | 270 + 10 Pills | 443.96€ 422.82€ | |
| Cialis Generic | 40mg | 10 Pills | 37.79€ 35.99€ | |
| Cialis Black | 80mg | 60 + 4 Pills | 150.98€ 143.79€ | |
| Cialis Generic | 20mg | 180 + 10 Pills | 254.09€ 241.99€ | |
| Cialis Generic | 2.5mg | 10 Pills | 28.51€ 27.15€ | |
| Cialis Professional | 40mg | 90 + 2 Pills | 348.59€ 331.99€ | |
| Cialis Generic | 5mg | 10 Pills | 29.39€ 27.99€ | |
| Cialis Professional | 40mg | 120 + 4 Pills | 436.68€ 415.89€ | |
| Cialis Generic | 5mg | 270 + 10 Pills | 205.81€ 196.01€ |
In dogs, an increased incidence of disseminated arteritis was observed in 1- and 6-month studies at unbound tadalafil exposure of 1- to 54-fold above the human exposure (AUC) at the MRHD of 20 mg. In a 12-month dog study, no disseminated arteritis was observed, but 2 dogs exhibited marked decreases in white blood cells (neutrophils) and moderate decreases in platelets with inflammatory signs at unbound tadalafil exposures of approximately14- to 18-fold the human exposure at the MRHD of 20 mg.
The abnormal blood-cell findings were reversible within 2 weeks after stopping treatment.
| Benefit | Description | Evidence / Notes |
|---|---|---|
| Spontaneous activity | No need to plan medication timing | User reports and studies show improved spontaneity |
| Lower side effect risk | Regular low doses may reduce side effects | Compared to on-demand dosing |
| Improved quality of life | Greater sexual confidence and reduced anxiety | Patient surveys |
| Long-term safety | Long-term usage appears safe for most users | Ongoing research |
The efficacy and safety of tadalafil in the treatment of erectile dysfunction has been evaluated in 22 clinical trials of up to 24-weeks duration, involving over 4000 patients.
The mean oral clearance for tadalafil is 2.5 L/hr and the mean terminal half-life is 17.5 hours in healthy subjects. Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose). Healthy male elderly subjects (65 years or over) had a lower oral clearance of tadalafil, resulting in25% higher exposure (AUC) with no effect on Cmax relative to that observed in healthy subjects 19 to 45 years of age. However, greater sensitivity to medications winsome older individuals should be considered [see Use In Specific Populations] . In male patients with diabetes mellitus after a 10 mg tadalafil dose, exposure(AUC) was reduced approximately 19% and Cmax was 5% lower than that observed in healthy subjects. CIALIS, when taken as needed up to once per day, was shown to be effective in improving erectile function in men with erectile dysfunction (ED).
Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil10 mg in subjects taking bendrofluazide was 6/4 mm Hg, compared to placebo. A study was conducted to assess the interaction of enalapril (10 to 20 mg daily) and tadalafil10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking enalapril was 4/1 mm Hg, compared to placebo. A study was conducted to assess the interaction of sustained-release metoprolol (25 to 200 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking metoprolol was 5/3 mm Hg, compared to placebo.
Alcohol and PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. The interaction of tadalafil with alcohol was evaluated in 3 clinical pharmacology studies. In 2 of these, alcohol was administered at a dose of 0.7 g/kg, which is equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male, and tadalafil was administered at a dose of 10 mg in one study and 20 mg in another. In both these studies, all patients imbibed the entire alcohol dose within 10 minutes of starting. In one of these two studies, blood alcohol levels of 0.08% were confirmed.
In these two studies, more patients had clinically significant decreases in blood pressure on the combination of tadalafil and alcohol as compared to alcohol alone. Some subjects reported postural dizziness, and orthostatic hypotension was observed in some subjects. When tadalafil 20 mg was administered with a lower dose of alcohol (0.6 g/kg, which is equivalent to approximately 4 ounces of 80-proofvodka, administered in less than 10 minutes), orthostatic hypotension was not observed, dizziness occurred with similar frequency to alcohol alone, and the hypotensive effects of alcohol were not potentiated. The effects of tadalafil on cardiac function, hemodynamics, and exercise tolerance were investigated in a single clinical pharmacology study. In this blinded crossover trial, 23 subjects with stable coronary artery disease and evidence of exercise-induced cardiac ischemia were enrolled. CIALIS was studied in the general ED population in 7 randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design, primary efficacy and safety studies of 12-weeks duration. Two of these studies were conducted in the United States and 5 were conducted in centers outside the US.
Additional efficacy and safety studies were performed in ED patients with diabetes mellitus and in patients who developed ED status post bilateral nerve-sparing radical prostatectomy.
In these 7 trials, CIALIS was taken as needed, at doses ranging from 2.5 to 20 mg, up to once per day. Patients were free to choose the time interval between dose administration and the time of sexual attempts.
| Dosage (mg) | Recommended for | Frequency | Notes |
|---|---|---|---|
| 2.5 mg | Patients with mild ED or as prevention | Once daily | Often taken in the morning |
| 5 mg | Moderate ED, active lifestyle | Once daily | Consistent daily intake |
| 10 mg | Not typical for daily use | As needed (not daily) | Higher dose, used occasionally |
| 20 mg | Not recommended for daily use | As needed | Higher doses are not daily |
Food and alcohol intake were not restricted.
The mean change in QT (Individual QTcorrection) for tadalafil, relative to placebo, was 2.8 milliseconds (two-sided 90% CI=1.2, 4.4). A 100-mg dose of tadalafil (5 times the highest recommended dose) was chosen because this dose yields exposures covering those observed upon coadministration of tadalafil with potent CYP3A4 inhibitors or those observed in renal impairment. In this study, the mean increase in heart rate associated with a 100-mg dose of tadalafil compared to placebo was 3.1 beats per minute. Over a dose range of 2.5 to 20 mg, tadalafil exposure (AUC) increases proportionally with dose in healthy subjects. Steady-state plasma concentrations are attained within 5 days of once per day dosing and exposure is approximately 1.6-fold greater than after a single dose.
Mean tadalafil concentrations measured after the administration of a single oral dose of 20 mg and single and once daily multiple doses of 5 mg, from a separate study, ( see Figure 4) to healthy male subjects are depicted in Figure 4 . Figure 4: Plasma tadalafil concentrations (mean ± SD) following a single 20-mg tadalafil dose and single and once daily multiple doses of 5 mg After single oral-dose administration, the maximum observed plasma concentration (C) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined. The rate and extent of absorption of tadalafil are not influenced by food; thus is cialis generic CIALIS may be taken with or without food. The mean apparent volume of distribution following oral administration is approximately 63 L, indicating that tadalafil is distributed into tissues.
At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins. Less than 0.0005% of the administered dose appeared in the semen of healthy subjects. Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methyl catechol and methyl catechol glucuronide conjugate, respectively. In vitro data suggests that metabolites are not expected to be pharmacologically active at observed metabolite concentrations. Several assessment tools were used to evaluate the effect of CIALIS on erectile function. The 3 primary outcome measures were the Erectile Function (EF) domain of the International Index of Erectile Function(IIEF) and Questions 2 and 3 from Sexual Encounter Profile (SEP).