Systemic drug exposures, as measured by AUC of unbound tadalafil, were approximately 10-fold for mice, and 14-and 26-fold for male and female rats, respectively, the exposures in human males given Maximum Recommended Human Dose (MRHD) of 20 mg. Mutagenesis— Tadalafil was not mutagenic in the in vitrobacterial Ames assays or the forward mutation test in mouse lymphoma cells. Impairment of Fertility— There were no effects on fertility, reproductive performance or reproductive organ morphology in male or female rats given oral doses of tadalafil up to 400 mg/kg/day, a dose producing AUCs for unbound tadalafil of 14-fold for males or 26-fold for females the exposures observed in human males given the MRHD of 20 mg. Systemic exposure (based on AUC) at no-observed-adverse-effect-level (NOAEL) (10 mg/kg/day) for unbound tadalafil was similar to that expected in humans at the MRHD of 20 mg. There were no treatment-related testicular findings in rats or mice treated with doses up to 400 mg/kg/day for 2 years. Animal studies showed vascular inflammation in tadalafil-treated mice, rats, and dogs.
- PDE5 inhibitors are contraindicated in patients using nitrates.
- Nitrates can be found in some heart medications and recreational drugs.
- Concomitant use can cause a dangerous, potentially fatal, drop in BP.
- Always carry a list of your medications in case of emergency.
- Inform new doctors or dentists before any procedure or new prescription.
- Consider a medical alert bracelet if on multiple cardiovascular drugs.
14 CLINICAL STUDIES 14.1 Tadalafil Tablets for Use as Needed for EDThe 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. Tadalafil tablets, when taken as needed up to once per day, was shown to be effective in improving erectile function in men with erectile dysfunction (ED).Tadalafil tablets were 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, tadalafil tablets were 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. Food and alcohol intake were not restricted.Several assessment tools were used to evaluate the effect of tadalafil tablets on erectile function.
14.2 Tadalafil Tablets for Once Daily Use for ED
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). The IIEF is a 4-week recall questionnaire that was administered at the end of a treatment-free baseline period and subsequently at follow-up visits after randomization. The IIEF EF tadalafil 5mg domain has a 30-point total score, where higher scores reflect better erectile function. SEP is a diary in which patients recorded each sexual attempt made throughout the study. SEP Question 2 asks, “Were you able to insert your penis into the partner’s vagina?” SEP Question 3 asks, “Did your erection last long enough for you to have successful intercourse?” The overall percentage of successful attempts to insert the penis into the vagina (SEP2) and to maintain the erection for successful intercourse (SEP3) is derived for each patient.Results in ED Population in US Trials— The 2 primary US efficacy and safety trials included a total of 402 men with erectile dysfunction, with a mean age of 59 years (range 27 to 87 years). The population was 78% White, 14% Black, 7% Hispanic, and 1% of other ethnicities, and included patients with ED of various severities, etiologies (organic, psychogenic, mixed), and with multiple co-morbid conditions, including diabetes mellitus, hypertension, and other cardiovascular disease. Most (>90%) patients reported ED of at least 1-year duration. Study A was conducted primarily in academic centers. Study B was conducted primarily in community-based urology practices.
- Available as round, yellow, film-coated tablets imprinted with "10".
- Manufactured by various companies (e.g., Ajanta, Aurobindo, Teva).
- Generic tadalafil is bioequivalent to the brand-name drug.
- Check pill identification resources if unsure of medication.
- Report any suspected adverse reactions to the FDA or equivalent.
- Keep out of reach of children and pets.
In each of these 2 trials, tadalafil tablets 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables ( seeTable 11).
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Cialis Generic | 5mg | 60 + 4 Pills | 86.02€ 81.92€ | |
| Tadalista Super Active | 20mg | 120 + 16 Pills | 382.15€ 363.95€ | |
| Cialis Generic | 60mg | 60 + 4 Pills | 145.06€ 138.15€ | |
| Cialis Generic | 40mg | 30 + 4 Pills | 74.97€ 71.40€ | |
| Cialis Generic | 2.5mg | 90 + 6 Pills | 112.43€ 107.08€ | |
| Cialis Generic | 20mg | 10 Pills | 31.49€ 29.99€ | |
| Cialis Generic | 10mg | 10 Pills | 31.41€ 29.91€ | |
| Cialis Generic | 10mg | 360 + 10 Pills | 388.49€ 369.99€ | |
| Cialis Generic | 2.5mg | 20 Pills | 40.73€ 38.79€ | |
| Cialis Generic | 60mg | 30 + 2 Pills | 85.33€ 81.27€ | |
| Cialis Generic | 10mg | 30 + 4 Pills | 63.32€ 60.30€ | |
| Tadalista Super Active | 20mg | 20 + 4 Pills | 92.35€ 87.95€ | |
| Cialis Generic | 40mg | 360 + 10 Pills | 477.87€ 455.11€ | |
| Cialis Generic | 20mg | 60 + 6 Pills | 117.76€ 112.15€ |
The treatment effect of tadalafil tablets did not diminish over time.Table 11: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in the Two Primary US TrialsResults in General ED Population in Trials Outside the US— The 5 primary efficacy and safety studies conducted in the general ED population outside the US included 1112 patients, with a mean age of 59 years (range 21 to 82 years).
| Parameter | Value | Description |
|---|---|---|
| Absorption Rate | Rapid | Peaks in about 2 hours |
| Bioavailability | 80% | Percentage absorbed into bloodstream |
| Half-life | 17.5 hours | How long the drug stays active |
| Metabolism | Liver via CYP3A4 | Hepatic processing |
| Excretion | Feces and urine | Mainly via feces |
The population was 76% White, 1% Black, 3% Hispanic, and 20% of other ethnicities, and included patients with ED of various severities, etiologies (organic, psychogenic, mixed), and with multiple co-morbid conditions, including diabetes mellitus, hypertension, and other cardiovascular disease.
Section snippets
Systemic drug exposures, as measured by AUC of unbound tadalafil, were approximately 10-fold for mice, and 14-and 26-fold for male and female rats, respectively, the exposures in human males given Maximum Recommended Human Dose (MRHD) of 20 mg. Mutagenesis— Tadalafil was not mutagenic in the in vitrobacterial Ames assays or the forward mutation test in mouse lymphoma cells. Impairment of Fertility— There were no effects on fertility, reproductive performance or reproductive organ morphology in male or female rats given oral doses of tadalafil up to 400 mg/kg/day, a dose producing AUCs for unbound tadalafil of 14-fold for males or 26-fold for females the exposures observed in human males given the MRHD of 20 mg. Systemic exposure (based on AUC) at no-observed-adverse-effect-level (NOAEL) (10 mg/kg/day) for unbound tadalafil was similar to that expected in humans at the MRHD of 20 mg. There were no treatment-related testicular findings in rats or mice treated with doses up to 400 mg/kg/day for 2 years.
Tadalafil 40 mg: How long does it last?
Animal studies showed vascular inflammation in tadalafil-treated mice, rats, and dogs. 14 CLINICAL STUDIES 14.1 Tadalafil Tablets for Use as Needed for EDThe 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. Tadalafil tablets, when taken as needed up to once per day, was shown to be effective in improving erectile function in men with erectile dysfunction (ED).Tadalafil tablets were 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, tadalafil tablets were taken as needed, at doses ranging from 2.5 to 20 mg, up to once per day.
What is tadalafil (generic Cialis®)
Patients were free to choose the time interval between dose administration and the time of sexual attempts. Food and alcohol intake were not restricted.Several assessment tools were used to evaluate the effect of tadalafil tablets 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). The IIEF is a 4-week recall questionnaire that was administered at the end of a treatment-free baseline period and subsequently at follow-up visits after randomization. The IIEF EF tadalafil 5mg domain has a 30-point total score, where higher scores reflect better erectile function. Most (90%) patients reported ED of tadalafil sale at least 1-year duration.
| Advice | Details | Rationale |
|---|---|---|
| Take as directed | Follow prescription instructions | Ensures safety and efficacy |
| Avoid heavy meals before taking | Especially fatty foods | May delay onset of action |
| Do not combine with nitrates | To prevent severe hypotension | Life-threatening interaction |
| Limit alcohol consumption | Excessive alcohol may impair effectiveness | Reduces risk of side effects |
| Report side effects to doctor | Especially vision changes or chest pain | For prompt medical attention |
In these 5 trials, tadalafil tablets 5, 10, and 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables ( seeTables 12, 13 and 14). The treatment effect of tadalafil tablets did not diminish over time.Table 12: Mean Endpoint and Change from Baseline for the EF Domain of the IIEF in the General ED Population in Five Primary Trials Outside the USTable 13: Mean Post-Baseline Success Rate and Change from Baseline for SEP Question 2 (“Were you able to insert your penis into the partner’s vagina?”) in the General ED Population in Five Pivotal Trials Outside the USTable 14: Mean Post-Baseline Success Rate and Change from Baseline for SEP Question 3 (“Did your erection last long enough for you to have successful intercourse?”) in the General ED Population in Five Pivotal Trials Outside the USIn addition, there were improvements in EF domain scores, success rates based upon SEP Questions 2 and 3, and patient-reported improvement in erections across patients with ED of all degrees of disease severity while taking tadalafil tablets, compared to patients on placebo.Therefore, in all 7 primary efficacy and safety studies, tadalafil tablets showed statistically significant improvement in patients’ ability to achieve an erection sufficient for vaginal penetration and to maintain the erection long enough for successful intercourse, as measured by the IIEF questionnaire and by SEP diaries.Efficacy Results in ED Patients with Diabetes Mellitus— Tadalafil tablets were shown to be effective in treating ED in patients with diabetes mellitus. Patients with diabetes were included in all 7 primary efficacy studies in the general ED population (N=235) and in one study that specifically assessed tadalafil tablets in ED patients with type 1 or type 2 diabetes (N=216).
- Tadalafil is a PDE5 inhibitor, similar to sildenafil (Viagra).
- Longer half-life than sildenafil, allowing for less frequent dosing.
- Can be used for both "as-needed" and daily dosing regimens.
- Not intended for use by women or children.
- Safety and efficacy in men under 18 have not been established.
- A lower 5 mg daily dose is often used for maintenance.
In this randomized, placebo-controlled, double-blinded, parallel-arm design prospective trial, tadalafil tablets demonstrated clinically meaningful and statistically significant improvement in erectile function, as measured by the EF domain of the IIEF questionnaire and Questions 2 and 3 of the SEP diary ( seeTable 15).Table 15: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Study in ED Patients with DiabetesEfficacy Results in ED Patients following Radical Prostatectomy— Tadalafil tablets were shown to be effective in treating patients who developed ED following bilateral nerve-sparing radical prostatectomy. In 1 randomized, placebo-controlled, double-blinded, parallel-arm design prospective trial in this population (N=303), tadalafil tablets demonstrated clinically meaningful and statistically significant improvement in erectile function, as measured by the EF domain of the IIEF questionnaire and Questions 2 and 3 of the SEP diary ( seeTable 16).Table 16: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Study in Patients who Developed ED Following Bilateral Nerve-Sparing Radical ProstatectomyResults in Studies to Determine the Optimal Use of Tadalafil Tablets— Several studies were conducted with the objective of determining the optimal use of tadalafil tablets in the treatment of ED. In one of these studies, the percentage of patients reporting successful erections within 30 minutes of dosing was determined. In this randomized, placebo-controlled, double-blinded trial, 223 patients were randomized to placebo, tadalafil tablets 10, or 20 mg. Using a stopwatch, patients recorded the time following dosing at which a successful erection was obtained. A successful erection was defined as at least 1 erection in 4 attempts that led to successful intercourse.
Read Real Stories of Men who Underwent Treatment for ED at New York Urology Specialists.
In one of these studies, the percentage of patients reporting successful erections within 30 minutes of dosing was determined. In this randomized, placebo-controlled, double-blinded trial, 223 patients were randomized to placebo, tadalafil tablets 10, or 20 mg. Using a stopwatch, patients recorded the time following dosing at which a successful erection was obtained. A successful erection was defined as at least 1 erection in 4 attempts that led to successful intercourse. At or prior to 30 minutes, 35% (26/74), 38% (28/74), and 52% (39/75) of patients in the placebo, 10-, and 20-mg groups, respectively, reported successful erections as defined above.Two studies were conducted to assess the efficacy of tadalafil tablets at a given timepoint after dosing, specifically at 24 hours and at 36 hours after dosing.In the first of these studies, 348 patients with ED were randomized to placebo or tadalafil tablets 20 mg.
Efficacy and safety daily tadalafil in men with erectile dysfunction previously unresponsive to on-demand tadalafil
Patients were encouraged to make 4 total attempts at intercourse; 2 attempts were to occur at 24 hours after dosing and 2 completely separate attempts were to occur at 36 hours after dosing. The results demonstrated a difference between the placebo group and the tadalafil tablets group at each of the pre-specified timepoints. At the 24-hour timepoint, (more specifically, 22 to 26 hours), 53/144 (37%) patients reported at least 1 successful intercourse in the placebo group versus 84/138 (61%) in the tadalafil tablets 20-mg group. At the 36-hour timepoint (more specifically, 33 to 39 hours), 49/133 (37%) of patients reported at least 1 successful intercourse in the placebo group versus 88/137 (64%) in the tadalafil tablets 20-mg group.In the second of these studies, a total of 483 patients were evenly randomized to 1 of 6 groups: 3 different dosing groups (placebo, tadalafil tablets 10, or 20 mg) that were instructed to attempt intercourse at 2 different times (24 and 36 hours post-dosing). At or prior to 30 minutes, 35% (26/74), 38% (28/74), and 52% (39/75) of patients in the placebo, 10-, and 20-mg groups, respectively, reported successful erections as defined above.Two studies were conducted to assess the efficacy of tadalafil tablets at a given timepoint after dosing, specifically at 24 hours and at 36 hours after dosing.In the first of these studies, 348 patients with ED were randomized to placebo or tadalafil tablets 20 mg.
- Can be part of a treatment plan for psychological ED.
- Success with medication can help break the cycle of anxiety.
- May be used on an occasional basis for situational ED.
- Useful for men who desire spontaneity due to long duration.
- Not suitable for everyone; a thorough medical history is essential.
- Discuss all treatment options, benefits, and risks with your doctor.
Patients were encouraged to make 4 total attempts at intercourse; 2 attempts were to occur at 24 hours after dosing and 2 completely separate attempts were to occur at 36 hours after dosing.
| Storage Condition | Temperature Range | Light Exposure | Shelf Life | Additional Notes |
|---|---|---|---|---|
| Room Temperature | 20-25°C | Keep in original container | 2-3 years | Keep away from moisture and heat |
| Protect from Light | Yes | Yes | Store in a cool, dry place | |
| Keep Out of Reach of Children | Yes | Essential safety measure |
The results demonstrated a difference between the placebo group and the tadalafil tablets group at each of the pre-specified timepoints. At the 24-hour timepoint, (more specifically, 22 to 26 hours), 53/144 (37%) patients reported at least 1 successful intercourse in the placebo group versus 84/138 (61%) in the tadalafil tablets 20-mg group.
5.7 Renal Impairment
SEP is a diary in which patients recorded each sexual attempt made throughout the study. SEP Question 2 asks, “Were you able to insert your penis into the partner’s vagina?” SEP Question 3 asks, “Did your erection last long enough for you to have successful intercourse?” The overall percentage of successful attempts to insert the penis into the vagina (SEP2) and to maintain the erection for successful intercourse (SEP3) is derived for each patient.Results in ED Population in US Trials— The 2 primary US efficacy and safety trials included a total of 402 men with erectile dysfunction, with a mean age of 59 years (range 27 to 87 years). The population was 78% White, 14% Black, 7% Hispanic, and 1% of other ethnicities, and included patients with ED of various severities, etiologies (organic, psychogenic, mixed), and with multiple co-morbid conditions, including diabetes mellitus, hypertension, and other cardiovascular disease. Most (>90%) patients reported ED of at least 1-year duration. Study A was conducted primarily in academic centers.
J Sex Med
Study B was conducted primarily in community-based urology practices. In each of these 2 trials, tadalafil tablets 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables ( seeTable 11). The treatment effect of tadalafil tablets did not diminish over time.Table 11: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in the Two Primary US TrialsResults in General ED Population in Trials Outside the US— The 5 primary efficacy and safety studies conducted in the general ED population outside the US included 1112 patients, with a mean age of 59 years (range 21 to 82 years). The population was 76% White, 1% Black, 3% Hispanic, and 20% of other ethnicities, and included patients with ED of various severities, etiologies (organic, psychogenic, mixed), and with multiple co-morbid conditions, including diabetes mellitus, hypertension, and other cardiovascular disease. Most (90%) patients reported ED of tadalafil sale at least 1-year duration.
What are the serious side effects of tadalafil?
In these 5 trials, tadalafil tablets 5, 10, and 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables ( seeTables 12, 13 and 14). The treatment effect of tadalafil tablets did not diminish over time.Table 12: Mean Endpoint and Change from Baseline for the EF Domain of the IIEF in the General ED Population in Five Primary Trials Outside the USTable 13: Mean Post-Baseline Success Rate and Change from Baseline for SEP Question 2 (“Were you able to insert your penis into the partner’s vagina?”) in the General ED Population in Five Pivotal Trials Outside the USTable 14: Mean Post-Baseline Success Rate and Change from Baseline for SEP Question 3 (“Did your erection last long enough for you to have successful intercourse?”) in the General ED Population in Five Pivotal Trials Outside the USIn addition, there were improvements in EF domain scores, success rates based upon SEP Questions 2 and 3, and patient-reported improvement in erections across patients with ED of all degrees of disease severity while taking tadalafil tablets, compared to patients on placebo.Therefore, in all 7 primary efficacy and safety studies, tadalafil tablets showed statistically significant improvement in patients’ ability to achieve an erection sufficient for vaginal penetration and to maintain the erection long enough for successful intercourse, as measured by the IIEF questionnaire and by SEP diaries.Efficacy Results in ED Patients with Diabetes Mellitus— Tadalafil tablets were shown to be effective in treating ED in patients with diabetes mellitus. Patients with diabetes were included in all 7 primary efficacy studies in the general ED population (N=235) and in one study that specifically assessed tadalafil tablets in ED patients with type 1 or type 2 diabetes (N=216). In this randomized, placebo-controlled, double-blinded, parallel-arm design prospective trial, tadalafil tablets demonstrated clinically meaningful and statistically significant improvement in erectile function, as measured by the EF domain of the IIEF questionnaire and Questions 2 and 3 of the SEP diary ( seeTable 15).Table 15: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Study in ED Patients with DiabetesEfficacy Results in ED Patients following Radical Prostatectomy— Tadalafil tablets were shown to be effective in treating patients who developed ED following bilateral nerve-sparing radical prostatectomy. In 1 randomized, placebo-controlled, double-blinded, parallel-arm design prospective trial in this population (N=303), tadalafil tablets demonstrated clinically meaningful and statistically significant improvement in erectile function, as measured by the EF domain of the IIEF questionnaire and Questions 2 and 3 of the SEP diary ( seeTable 16).Table 16: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Study in Patients who Developed ED Following Bilateral Nerve-Sparing Radical ProstatectomyResults in Studies to Determine the Optimal Use of Tadalafil Tablets— Several studies were conducted with the objective of determining the optimal use of tadalafil tablets in the treatment of ED. At the 36-hour timepoint (more specifically, 33 to 39 hours), 49/133 (37%) of patients reported at least 1 successful intercourse in the placebo group versus 88/137 (64%) in the tadalafil tablets 20-mg group.In the second of these studies, a total of 483 patients were evenly randomized to 1 of 6 groups: 3 different dosing groups (placebo, tadalafil tablets 10, or 20 mg) that were instructed to attempt intercourse at 2 different times (24 and 36 hours post-dosing).