DRUG INTERACTIONS
Tadalafil tablets, when taken once daily, 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 2 randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design, primary efficacy and safety studies of 12-and 24-weeks duration, respectively. One of these studies was conducted in the United States and one was conducted in centers outside the US. An additional efficacy and safety study was performed in ED patients with diabetes mellitus. Tadalafil tablets were taken once daily at doses ranging from 2.5 to 10 mg.
- Onset of action for on-demand use is typically 30-45 minutes.
- Maximum plasma concentration is reached within 2 hours.
- High-fat meal can delay time to maximum concentration.
- The 36-hour window does not mean an erection lasts that long.
- It means the ability to get an erection when stimulated is possible.
- Daily dosing leads to steady-state concentration in about 5 days.
Food and alcohol intake were not restricted. Timing of sexual activity was not restricted relative to when patients took tadalafil tablets.Results in General ED Population— The primary US efficacy and safety trial included a total of 287 patients, with a mean age of 59 years (range 25 to 82 years). The population was 86% White, 6% Black, 6% Hispanic, and 2% 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 (>96%) patients reported ED of at least 1-year duration.The primary efficacy and safety study conducted outside the US included 268 patients, with a mean age of 56 years (range 21 to 78 years). The population was 86% White, 3% Black, 0.4% Hispanic, and 10% 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. Ninety-three percent of patients reported ED of at least 1-year duration.In each of these trials, conducted without regard to the timing of dose and sexual intercourse, tadalafil for premature ejaculation 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 17). When taken as directed, tadalafil tablets were effective at improving erectile function.In the 6 month double-blind study, the treatment effect of tadalafil tablets did not diminish over time.Table 17: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in the Two Tadalafil Tablets for Once Daily Use StudiesEfficacy Results in ED Patients with Diabetes Mellitus— Tadalafil tablets for once daily use was shown to be effective in treating ED in patients with diabetes mellitus.
The recommended dose
When taken as directed, tadalafil tablets were effective at improving erectile function.In the 6 month double-blind study, the treatment effect of tadalafil tablets did not diminish over time.Table 17: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in the Two Tadalafil Tablets for Once Daily Use StudiesEfficacy Results in ED Patients with Diabetes Mellitus— Tadalafil tablets for once daily use was shown to be effective in treating ED in patients with diabetes mellitus. Patients with diabetes were included in both studies in the general ED population (N=79). A third randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design trial included only ED patients with type 1 or type 2 diabetes (N=298). In this third 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 18).Table 18: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Tadalafil Tablets for Once Daily Use Study in ED Patients with Diabetes14.3 Tadalafil Tablets 5 mg for Once Daily Use for Benign Prostatic Hyperplasia (BPH)The efficacy and safety of tadalafil tablets for once daily use for the treatment of the signs and symptoms of BPH was evaluated in 3 randomized, multinational, double-blinded, placebo-controlled, parallel-design, efficacy and safety studies of 12 weeks duration. Two of these studies were in men with BPH and one study was specific to men with both ED and BPH [see Clinical Studies ( 14.4)] .
Who should not use tadalafil?
The first study (Study J) randomized 1058 patients to receive either tadalafil tablets 2.5 mg, 5 mg, 10 mg or 20 mg for once daily use or placebo. The second study (Study K) randomized 325 patients to receive either tadalafil tablets 5 mg for once daily use or placebo. The full study population was 87% White, 2% Black, 11% other races; 15% was of Hispanic ethnicity. Patients with multiple co-morbid conditions such as diabetes mellitus, hypertension, and other cardiovascular disease were included.The primary efficacy endpoint in the two studies that evaluated the effect of tadalafil tablets for the signs and symptoms of BPH was the International Prostate Symptom Score (IPSS), a four week recall questionnaire that was administered at the beginning and end of a placebo run-in period and subsequently at follow-up visits after randomization. The IPSS assesses the severity of irritative (frequency, urgency, nocturia) and obstructive symptoms (incomplete emptying, stopping and starting, weak stream, and pushing or straining), with scores ranging from 0 to 35; higher numeric scores representing greater severity. Patients with diabetes were included in both studies in the general ED population (N=79). A third randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design trial included only ED patients with type 1 or type 2 diabetes (N=298).
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Cialis Generic | 2.5mg | 30 + 4 Pills | 51.95€ 49.48€ | |
| Cialis Generic | 60mg | 20 Pills | 65.61€ 62.49€ | |
| Cialis Generic | 10mg | 10 Pills | 31.41€ 29.91€ | |
| Cialis Generic | 20mg | 270 + 10 Pills | 335.21€ 319.25€ | |
| Cialis Generic | 40mg | 10 Pills | 37.79€ 35.99€ | |
| Cialis Generic | 60mg | 120 + 8 Pills | 240.18€ 228.74€ | |
| Cialis Generic | 5mg | 30 + 4 Pills | 53.56€ 51.01€ | |
| Cialis Generic | 5mg | 90 + 6 Pills | 115.91€ 110.39€ | |
| Cialis Generic | 5mg | 20 Pills | 41.99€ 39.99€ | |
| Cialis Generic | 60mg | 10 Pills | 41.22€ 39.26€ | |
| Cialis Generic | 2.5mg | 360 + 10 Pills | 260.03€ 247.65€ | |
| Tadalista Super Active | 20mg | 180 + 20 Pills | 521.59€ 496.75€ | |
| Cialis Generic | 20mg | 180 + 10 Pills | 254.09€ 241.99€ | |
| Tadalista Super Active | 20mg | 60 + 8 Pills | 230.32€ 219.35€ |
In this third 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 18).Table 18: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Tadalafil Tablets for Once Daily Use Study in ED Patients with Diabetes14.3 Tadalafil Tablets 5 mg for Once Daily Use for Benign Prostatic Hyperplasia (BPH)The efficacy and safety of tadalafil tablets for once daily use for the treatment of the signs and symptoms of BPH was evaluated in 3 randomized, multinational, double-blinded, placebo-controlled, parallel-design, efficacy and safety studies of 12 weeks duration.
8.4 Pediatric Use
Tadalafil tablets with finasteride (N=203) was compared to placebo with finasteride (N=201). A statistically significant improvement from baseline (tadalafil tablets/finasteride 13.7, placebo/finasteride 15.1) was observed at week 4 (tadalafil tablets/finasteride 3.7, placebo/finasteride -1.1; p<.001), week 12 (tadalafil tablets/finasteride 4.7, placebo/finasteride 0.6; p<.001), and week 26 (tadalafil tablets/finasteride 4.7, placebo/finasteride 0.0; p<.001).14.4 Tadalafil Tablets 5 mg for Once Daily Use for ED and BPHThe efficacy and safety of tadalafil tablets for once daily use for the treatment of ED, and the signs and symptoms of BPH, in patients with both conditions was evaluated in one placebo-controlled, multinational, double-blind, parallel-arm study which randomized 606 patients to receive either tadalafil tablets 2.5 mg, 5 mg, for once daily use or placebo. ED severity ranged from mild to severe and BPH severity ranged from moderate to severe. The full study population had a mean age of 63 years (range 45 to 83) and was 93% White, 4% Black, 3% other races; 16% were of Hispanic ethnicity. Patients with multiple co-morbid conditions such as diabetes mellitus, hypertension, and other cardiovascular disease were included.In this study, the co-primary endpoints were total IPSS and the Erectile Function (EF) domain score of the International Index of Erectile Function (IIEF).
2. Health conditions
One of the key secondary endpoints in this study was Question 3 of the Sexual Encounter Profile diary (SEP3). Timing of sexual activity was not restricted relative to when patients took tadalafil tablets.The efficacy results for patients with both ED and BPH, who received either tadalafil tablets 5 mg for once daily use or placebo (N=408) are shown in Tables 21 and 22 and Figure 8.Tadalafil tablets 5 mg for once daily use resulted in statistically significant improvements in the total IPSS and in the EF domain of the IIEF questionnaire. Two of these studies were in men with BPH and one study was specific to men with both ED and BPH [see Clinical Studies ( 14.4)] . The first study (Study J) randomized 1058 patients to receive either tadalafil tablets 2.5 mg, 5 mg, 10 mg or 20 mg for once daily use or placebo.
- Clinical trials demonstrated significant improvement over placebo.
- Effective in a broad range of ED severities and causes.
- Improvement in BPH symptoms can be seen within weeks.
- Long-term studies support safety of daily use for up to 2 years.
- Does not protect against sexually transmitted infections.
- Should be part of a broader approach to sexual health.
The second study (Study K) randomized 325 patients to receive either tadalafil tablets 5 mg for once daily use or placebo. The full study population was 87% White, 2% Black, 11% other races; 15% was of Hispanic ethnicity. Patients with multiple co-morbid conditions such as diabetes mellitus, hypertension, and other cardiovascular disease were included.The primary efficacy endpoint in the two studies that evaluated the effect of tadalafil tablets for the signs and symptoms of BPH was the International Prostate Symptom Score (IPSS), a four week recall questionnaire that was administered at the beginning and end of a placebo run-in period and subsequently at follow-up visits after randomization. The IPSS assesses the severity of irritative (frequency, urgency, nocturia) and obstructive symptoms (incomplete emptying, stopping and starting, weak stream, and pushing or straining), with scores ranging from 0 to 35; higher numeric scores representing greater severity. Maximum urinary flow rate (Q max), an objective measure of urine flow, was assessed as a secondary efficacy endpoint in Study J and as a safety endpoint in Study K.The results for BPH patients with moderate to severe symptoms and a mean age of 63.2 years (range 44 to 87) who received either tadalafil tablets 5 mg for once daily use or placebo (N=748) in Studies J and K are shown in Table 19 and Figures 5 and 6, respectively.In each of these 2 trials, tadalafil tablets 5 mg for once daily use resulted in statistically significant improvement in the total IPSS compared to placebo.
Treatment Options When Cialis Does Not Work Well
Tadalafil tablets, when taken once daily, 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 2 randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design, primary efficacy and safety studies of 12-and 24-weeks duration, respectively. One of these studies was conducted in the United States and one was conducted in centers outside the US. An additional efficacy and safety study was performed in ED patients with diabetes mellitus. Tadalafil tablets were taken once daily at doses ranging from 2.5 to 10 mg. Food and alcohol intake were not restricted.
An evaluation of an alternative dosing regimen with tadalafil, 3 times/week, for men with erectile dysfunction: SURE study in 14 European countries
Timing of sexual activity was not restricted relative to when patients took tadalafil tablets.Results in General ED Population— The primary US efficacy and safety trial included a total of 287 patients, with a mean age of 59 years (range 25 to 82 years). The population was 86% White, 6% Black, 6% Hispanic, and 2% 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 (>96%) patients reported ED of at least 1-year duration.The primary efficacy and safety study conducted outside the US included 268 patients, with a mean age of 56 years (range 21 to 78 years). The population was 86% White, 3% Black, 0.4% Hispanic, and 10% 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. Ninety-three percent of patients reported ED of at least 1-year duration.In each of these trials, conducted without regard to the timing of dose and sexual intercourse, tadalafil for premature ejaculation 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 17). Mean total IPSS showed a decrease starting at the first scheduled observation (4 weeks) in Study K and remained decreased through 12 weeks.Table 19: Mean IPSS Changes in BPH Patients in Two Tadalafil Tablets for Once Daily Use StudiesFigure 5: Mean IPSS Changes in BPH Patients by Visit in Study JFigure 6: Mean IPSS Changes in BPH Patients by Visit in Study KIn Study J, the effect of tadalafil tablets 5 mg once daily on maximum urinary flow rate (Q max) was evaluated as a secondary efficacy endpoint. Mean Q maxincreased from baseline in both the treatment and placebo groups (tadalafil tablets 5 mg: 1.6 mL/sec, placebo: 1.2 mL/sec); however, these changes were not significantly different between groups.In Study K, the effect of tadalafil tablets 5 mg once daily on Q maxwas evaluated as a safety endpoint.
| Side Effect | Commonality | Severity | Notes |
|---|---|---|---|
| Headache | Common | Mild to Moderate | Usually resolves without intervention |
| Flushing | Moderate | Mild | Due to vasodilation |
| Dyspepsia | Common | Mild | Stomach discomfort |
| Muscle Aches | Less common | Mild | May occur after dose |
| Vision Changes | Rare | Mild to Moderate | Blurred vision or color perception issues |
Mean Q maxincreased from baseline in both the treatment and placebo groups (tadalafil tablets 5 mg: 1.6 mL/sec, placebo: 1.1 mL/sec); however, these changes were not significantly different between groups.Efficacy Results in Patients with BPH initiating Tadalafil Tablets and Finasteride– Tadalafil tablets for once daily use initiated together with finasteride was shown to be effective in treating the signs and symptoms of BPH in men with an enlarged prostate (>30 cc) for up to 26 weeks. This additional double-blinded, parallel-design study of 26 weeks duration randomized 696 men to initiate either tadalafil tablets 5 mg with finasteride 5 mg or placebo with finasteride 5 mg. The study population had a mean age of 10mg tadalafil 64 years (range 46-86). Patients with multiple co-morbid conditions such as erectile dysfunction, diabetes mellitus, hypertension, and other cardiovascular disease were included.Tadalafil tablets with finasteride demonstrated statistically significant improvement in the signs and symptoms of BPH compared to placebo with finasteride, as measured by the total IPSS at 12 weeks, the primary study endpoint ( seeTable 20).
| Use Case | Description | Typical Usage |
|---|---|---|
| Erectile Dysfunction Treatment | Helps achieve/maintain erections | Taken as needed before sex |
| Benign Prostatic Hyperplasia (BPH) | Relieves urinary symptoms | Taken daily or as prescribed |
| Pulmonary Arterial Hypertension (off-label) | Off-label use in some cases | Under medical supervision |
| Enhancing Exercise Performance | Some anecdotal reports | Not approved, consult doctor first |
Key secondary endpoints demonstrated improvement in total IPSS starting at the first scheduled observation at week 4 (tadalafil tablets -4.0, placebo -2.3: p<.001) and the score remained decreased through 26 weeks (tadalafil tablets -5.5, placebo -4.5; p=.022).
| Country | Legal Status | Prescription Required | Notes |
|---|---|---|---|
| USA | Prescription-only | Yes | Approved for ED and BPH |
| UK | Prescription-only | Yes | Controlled medication |
| Canada | Prescription-only | Yes | Available via pharmacy |
| Australia | Prescription-only | Yes | Schedule 4 drug |
| India | Prescription required | Yes | Widely available |
However, the magnitude of the treatment difference between placebo/finasteride and tadalafil tablets/finasteride decreased from 1.7 points at Week 4 to 1.0 point at Week 26, as shown in Table 20 and in Figure 7. The incremental benefit of tadalafil tablets beyond 26 weeks is unknown.Table 20: Mean Total IPSS Changes in BPH Patients in a Tadalafil Tablets for Once Daily Use Study Together with FinasterideFigure 7: Mean Total IPSS Changes By Visit in BPH Patients Taking Tadalafil Tablets for Once Daily Use Together With FinasterideIn the 404 patients who had both ED and BPH at baseline, changes in erectile function were assessed as key secondary endpoints using the EF domain of the IIEF questionnaire. Tadalafil tablets with finasteride (N=203) was compared to placebo with finasteride (N=201). A statistically significant improvement from baseline (tadalafil tablets/finasteride 13.7, placebo/finasteride 15.1) was observed at week 4 (tadalafil tablets/finasteride 3.7, placebo/finasteride -1.1; p<.001), week 12 (tadalafil tablets/finasteride 4.7, placebo/finasteride 0.6; p<.001), and week 26 (tadalafil tablets/finasteride 4.7, placebo/finasteride 0.0; p<.001).14.4 Tadalafil Tablets 5 mg for Once Daily Use for ED and BPHThe efficacy and safety of tadalafil tablets for once daily use for the treatment of ED, and the signs and symptoms of BPH, in patients with both conditions was evaluated in one placebo-controlled, multinational, double-blind, parallel-arm study which randomized 606 patients to receive either tadalafil tablets 2.5 mg, 5 mg, for once daily use or placebo. ED severity ranged from mild to severe and BPH severity ranged from moderate to severe. The full study population had a mean age of 63 years (range 45 to 83) and was 93% White, 4% Black, 3% other races; 16% were of Hispanic ethnicity. Patients with multiple co-morbid conditions such as diabetes mellitus, hypertension, and other cardiovascular disease were included.In this study, the co-primary endpoints were total IPSS and the Erectile Function (EF) domain score of the International Index of Erectile Function (IIEF).
5.6 Alpha-blockers and Antihypertensives
Maximum urinary flow rate (Q max), an objective measure of urine flow, was assessed as a secondary efficacy endpoint in Study J and as a safety endpoint in Study K.The results for BPH patients with moderate to severe symptoms and a mean age of 63.2 years (range 44 to 87) who received either tadalafil tablets 5 mg for once daily use or placebo (N=748) in Studies J and K are shown in Table 19 and Figures 5 and 6, respectively.In each of these 2 trials, tadalafil tablets 5 mg for once daily use resulted in statistically significant improvement in the total IPSS compared to placebo. Mean total IPSS showed a decrease starting at the first scheduled observation (4 weeks) in Study K and remained decreased through 12 weeks.Table 19: Mean IPSS Changes in BPH Patients in Two Tadalafil Tablets for Once Daily Use StudiesFigure 5: Mean IPSS Changes in BPH Patients by Visit in Study JFigure 6: Mean IPSS Changes in BPH Patients by Visit in Study KIn Study J, the effect of tadalafil tablets 5 mg once daily on maximum urinary flow rate (Q max) was evaluated as a secondary efficacy endpoint. Mean Q maxincreased from baseline in both the treatment and placebo groups (tadalafil tablets 5 mg: 1.6 mL/sec, placebo: 1.2 mL/sec); however, these changes were not significantly different between groups.In Study K, the effect of tadalafil tablets 5 mg once daily on Q maxwas evaluated as a safety endpoint. Mean Q maxincreased from baseline in both the treatment and placebo groups (tadalafil tablets 5 mg: 1.6 mL/sec, placebo: 1.1 mL/sec); however, these changes were not significantly different between groups.Efficacy Results in Patients with BPH initiating Tadalafil Tablets and Finasteride– Tadalafil tablets for once daily use initiated together with finasteride was shown to be effective in treating the signs and symptoms of BPH in men with an enlarged prostate (>30 cc) for up to 26 weeks. This additional double-blinded, parallel-design study of 26 weeks duration randomized 696 men to initiate either tadalafil tablets 5 mg with finasteride 5 mg or placebo with finasteride 5 mg.
What should I do for a missed dose of tadalafil?
The study population had a mean age of 10mg tadalafil 64 years (range 46-86). Patients with multiple co-morbid conditions such as erectile dysfunction, diabetes mellitus, hypertension, and other cardiovascular disease were included.Tadalafil tablets with finasteride demonstrated statistically significant improvement in the signs and symptoms of BPH compared to placebo with finasteride, as measured by the total IPSS at 12 weeks, the primary study endpoint ( seeTable 20). Key secondary endpoints demonstrated improvement in total IPSS starting at the first scheduled observation at week 4 (tadalafil tablets -4.0, placebo -2.3: p<.001) and the score remained decreased through 26 weeks (tadalafil tablets -5.5, placebo -4.5; p=.022). However, the magnitude of the treatment difference between placebo/finasteride and tadalafil tablets/finasteride decreased from 1.7 points at Week 4 to 1.0 point at Week 26, as shown in Table 20 and in Figure 7. The incremental benefit of tadalafil tablets beyond 26 weeks is unknown.Table 20: Mean Total IPSS Changes in BPH Patients in a Tadalafil Tablets for Once Daily Use Study Together with FinasterideFigure 7: Mean Total IPSS Changes By Visit in BPH Patients Taking Tadalafil Tablets for Once Daily Use Together With FinasterideIn the 404 patients who had both ED and BPH at baseline, changes in erectile function were assessed as key secondary endpoints using the EF domain of the IIEF questionnaire. One of the key secondary endpoints in this study was Question 3 of the Sexual Encounter Profile diary (SEP3). Timing of sexual activity was not restricted relative to when patients took tadalafil tablets.The efficacy results for patients with both ED and BPH, who received either tadalafil tablets 5 mg for once daily use or placebo (N=408) are shown in Tables 21 and 22 and Figure 8.Tadalafil tablets 5 mg for once daily use resulted in statistically significant improvements in the total IPSS and in the EF domain of the IIEF questionnaire.
