8 USE IN SPECIFIC POPULATIONS

Geriatric — Healthy male elderly subjects (65 years or over) had a lower oral clearance of tadalafil, resulting in 25% 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 in some older individuals should be considered [see Use in Specific Populations (8.5)]. Pediatric — Tadalafil has not been evaluated in individuals less than 18 years old [see Use in Specific Populations (8.4)]. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityTadalafil was not carcinogenic to rats or mice when administered daily for 2 years at doses up to 400 mg/kg/day. 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.Tadalafil was not mutagenic in the in vitro bacterial Ames assays or the forward mutation test in mouse lymphoma cells. Tadalafil was not clastogenic in the in vitro chromosomal aberration test in human lymphocytes or the in vivo rat micronucleus assays.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. In beagle dogs given tadalafil daily for 3 to 12 months, there was treatment-related non-reversible degeneration and atrophy of the seminiferous tubular epithelium in the testes in 20-100% of the dogs that resulted in a decrease in spermatogenesis in 40-75% of the dogs at doses of ≥10 mg/kg/day. 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.13.2 Animal Toxicology and/or PharmacologyAnimal studies showed vascular inflammation in tadalafil-treated mice, rats, and dogs. 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. 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 approximately 14- to 18-fold the human exposure at the MRHD of 20 mg. The abnormal blood-cell findings were reversible within 2 weeks upon removal of the drug.Reproductive Toxicology StudiesReproduction studies have been performed in rats and mice at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg and have revealed no evidence of impaired fertility or harm to the fetus due to tadalafil. In addition, there was no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to pregnant rats or mice at exposures up to 11 times the MRHD during the period of major organ development.In a rat prenatal and postnatal development study at doses of 60, 200, and 1000 mg/kg, a reduction in postnatal survival of pups was observed.

• Cialis 10 mg is not suitable for everyone.
• Men with heart disease should discuss risk with a doctor.
• It’s essential to stay hydrated while taking Cialis.
• Avoid high-fat meals close to dosing time.
• Cialis may improve self-esteem and relationships.
• Overdose can cause significant health issues.
• Always adhere to the prescribed dosage.
• Cialis may be used in combination with psychotherapy.
• Effectiveness may improve with healthy lifestyle changes.
• Keep a medication diary to track effects.
• Report any persistent side effects immediately.

The no observed effect level (NOEL) for maternal toxicity was 200 mg/kg/day and for developmental toxicity was 30 mg/kg/day. This gives approximately 16 and 10 fold exposure multiples, respectively, of the human AUC for the MRHD of 20 mg.

• Cialis 10 mg is available in tablet form.
• It is non-urgent, planned use enhances experience.
• Be cautious about interactions with antihypertensives.
• The drug can cause mild stomach upset.
• Cialis’s effects can improve quality of life.
• Men should follow the doctor’s instructions strictly.
• It can be discontinued if it causes problematic side effects.
• Cialis is a prescription-exclusive medication.
• Check expiration dates before use.
• Use caution when driving or operating machinery.
• Always talk with your healthcare provider first.

Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats.Tadalafil and/or its metabolites were secreted into the milk in lactating rats at concentrations approximately 2.4-fold greater than found in the plasma. Tadalafil was not carcinogenic to rats or mice when administered daily for 2 years at doses up to 400 mg/kg/day.

12.1 Mechanism of Action

Geriatric — Healthy male elderly subjects (65 years or over) had a lower oral clearance of tadalafil, resulting in 25% 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 in some older individuals should be considered [see Use in Specific Populations (8.5)]. Pediatric — Tadalafil has not been evaluated in individuals less than 18 years old [see Use in Specific Populations (8.4)]. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityTadalafil was not carcinogenic to rats or mice when administered daily for 2 years at doses up to 400 mg/kg/day. 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.Tadalafil was not mutagenic in the in vitro bacterial Ames assays or the forward mutation test in mouse lymphoma cells.

Dosage adjustments

Tadalafil was not clastogenic in the in vitro chromosomal aberration test in human lymphocytes or the in vivo rat micronucleus assays.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. In beagle dogs given tadalafil daily for 3 to 12 months, there was treatment-related non-reversible degeneration and atrophy of the seminiferous tubular epithelium in the testes in 20-100% of the dogs that resulted in a decrease in spermatogenesis in 40-75% of the dogs at doses of ≥10 mg/kg/day. 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.13.2 Animal Toxicology and/or PharmacologyAnimal studies showed vascular inflammation in tadalafil-treated mice, rats, and dogs. 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. 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.

Less common

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 approximately 14- to 18-fold the human exposure at the MRHD of 20 mg. The abnormal blood-cell findings were reversible within 2 weeks upon removal of the drug.Reproductive Toxicology StudiesReproduction studies have been performed in rats and mice at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg and have revealed no evidence of impaired fertility or harm to the fetus due to tadalafil. In addition, there was no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to pregnant rats or mice at exposures up to 11 times the MRHD during the period of major organ development.In a rat prenatal and postnatal development study at doses of 60, 200, and 1000 mg/kg, a reduction in postnatal survival of pups was observed. The no observed effect level (NOEL) for maternal toxicity was 200 mg/kg/day and for developmental toxicity was 30 mg/kg/day. This gives approximately 16 and 10 fold exposure multiples, respectively, of the human AUC for the MRHD of 20 mg. 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. Tadalafil was not mutagenic in the in vitro bacterial Ames assays or the forward mutation test in mouse lymphoma cells. 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 la cialis 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.

• Cialis 10 mg can be effective for many men.
• Use caution when traveling with Cialis.
• Check with a healthcare provider about possible interactions.
• Certain foods can delay Cialis onset.
• Regular use can improve ED symptoms over time.
• Some men experience back pain as a side effect.
• Cialis is sometimes used off-label for lung hypertension.
• It is considered safe when used as directed.
• Discontinue use if adverse effects are severe.
• Cialis may be less effective with certain illnesses.
• Never share your medication with others.

The abnormal blood-cell findings were reversible within 2 weeks upon removal of the drug.

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Cialis Super Active	20mg	180 + 20 Pills	521.59€ 496.75€	Buy
Cialis Generic	20mg	20 Pills	54.72€ 52.11€	Buy
Cialis Original	20mg	22 + 2 Pills	129.20€ 123.05€	Buy
Cialis Professional	40mg	10 Pills	65.09€ 61.99€	Buy
Cialis Soft Tabs	20mg	60 + 4 Pills	159.37€ 151.78€	Buy
Cialis Generic	40mg	360 + 10 Pills	477.87€ 455.11€	Buy
Cialis Generic	40mg	120 + 8 Pills	206.98€ 197.12€	Buy
Cialis Generic	20mg	120 + 8 Pills	188.15€ 179.19€	Buy
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Cialis Professional	40mg	60 + 2 Pills	262.32€ 249.83€	Buy
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Reproduction studies have been performed in rats and mice at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg and have revealed no evidence of impaired fertility or harm to the fetus due to tadalafil. In addition, there was no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to pregnant rats or mice at exposures up to 11 times the MRHD during the period of major organ development. In a rat prenatal and postnatal development study at doses of 60, 200, and 1000 mg/kg, a reduction in postnatal survival of pups was observed. This gives approximately 16 and 10 fold exposure multiples, respectively, of the human AUC for the MRHD of 20 mg.

17.8 Alcohol

Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats.Tadalafil and/or its metabolites were secreted into the milk in lactating rats at concentrations approximately 2.4-fold greater than found in the plasma. Tadalafil was not carcinogenic to rats or mice when administered daily for 2 years at doses up to 400 mg/kg/day. 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. Tadalafil was not mutagenic in the in vitro bacterial Ames assays or the forward mutation test in mouse lymphoma cells. 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.

Mild side effects

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 la cialis 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. The abnormal blood-cell findings were reversible within 2 weeks upon removal of the drug. Reproduction studies have been performed in rats and mice at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg and have revealed no evidence of impaired fertility or harm to the fetus due to tadalafil.

What to do in case you take too much Cialis

In addition, there was no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to pregnant rats or mice at exposures up to 11 times the MRHD during the period of major organ development. In a rat prenatal and postnatal development study at doses of 60, 200, and 1000 mg/kg, a reduction in postnatal survival of pups was observed. This gives approximately 16 and 10 fold exposure multiples, respectively, of the human AUC for the MRHD of 20 mg. Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. Tadalafil and/or its metabolites were secreted into the milk in lactating rats at concentrations approximately 2.4-fold greater than found in the plasma. Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. Tadalafil and/or its metabolites were secreted into the milk in lactating rats at concentrations approximately 2.4-fold greater than found in the plasma. 14 CLINICAL STUDIES 14.1 CIALIS for Use as NeededThe 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. 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).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.

Aspect	Details	Frequency
Typical dose	10 mg per use	Once as needed
Recommended timing	30-60 minutes before sexual activity	-
Maximum frequency	Once per day	-
Onset of action	30-60 minutes	-
Duration of effect	Up to 36 hours	-
Food interaction	Can be taken with or without food	-

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 CIALIS on erectile function.

17.4 Potential for Drug Interactions When Taking CIALIS for Once Daily Use

14 CLINICAL STUDIES 14.1 CIALIS for Use as NeededThe 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. 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).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.

Mechanism of Action

Food and alcohol intake were not restricted.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). 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 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.

How does tadalafil work (mechanism of action)?

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. 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).

Benefits of Regenics: an Expert Medical Team Ensuring Safe and Personalized Care

In each of these 2 trials, CIALIS 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables (see Table 10). The treatment effect of CIALIS did not diminish over time.Results 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 at least 1-year duration. In these 5 trials, CIALIS 5, 10, and 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables (see Tables 11, 12 and 13). 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 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.

Parameter	Description	Notes
Effect on erectile function	Improves ability to achieve and sustain erection	Most effective within 30-60 mins
Response rate	About 80% of users find it effective	Varies by individual
Onset time	Usually within 30 minutes	Depends on food intake
Duration	Up to 36 hours	Long-lasting, effective window
Onset variation	Faster on empty stomach	Slower if taken after heavy meals

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. In each of these 2 trials, CIALIS 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables (see Table 10). The treatment effect of CIALIS did not diminish over time.Results 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 at least 1-year duration. In these 5 trials, CIALIS 5, 10, and 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables (see Tables 11, 12 and 13).

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