1.Tadalafil HISTORY
How was Tadalafil discovered?

The launch of Viagra, the world's first treatment for impotency, was an instant success.

Lilly ICOS (Eli Lilly and ICOS Corporation) have tapped into the vast demand for Viagra with Tadalafil, Viagra's direct competitor.

Tadalafil (tadalafil), a cyclic guanosine monophosphate (cGMP) was first discovered by some very smart scientists as the key to sustaining an erection.

They discovered that when a man gets sexually stimulated, a chain reaction occurs in the tissue of the penis that results in elevated levels of a substance called cyclic guanosine monophosphate (cGMP).

As long as there are sufficient levels of cGMP, the penis can remain erect.

That's how Tadalafil works - Tadalafil blocks the enzyme phosphodiesterase-5 (PDE5) which is responsible for the neutralization of cGMP. Tadalafil (tadalafil) is a highly selective inhibitor of PDE5. (PDE5 is not the only phosphodiesterase involved in the erectile physiology but it appears to be the most important one).

The efficacy and safety of Tadalafil was established in 22 clinical trials enrolling more than 4,000 patients. In 2 randomized, multicenter, double-blinded, placebo-controlled, 12-week studies, Tadalafil 20 mg was taken by patients enrolled from the general erectile dysfunction (ED) population.

More than one million patients have been treated with Tadalafil since its introduction in February 2003.

Tadalafil also demonstrated efficacy in ED patients with diabetes and in patients with ED following bilateral nerve-sparing radical prostatectomy. Tadalafil was shown to improve erectile function compared to placebo up to 36 hours post-dosing.

Note: World-drugs.net sells generic version of Tadalafil

2.Tadalafil FACTS

Tadalafil is a distinctive treatment for erectile dysfunction from the Lilly ICOS joint venture.

Lilly ICOS is a joint venture between pharmaceuticals giant Eli Lilly & Company and biotech firm ICOS. The company's only product is Tadalafil, a long-lasting treatment for erectile dysfunction.

Eli Lilly & Company has a heritage more than 128 years strong. Eli Lilly & Company was founded on May 10, 1876 by Colonel Eli Lilly in Indianapolis, Ind., in the Midwestern section of the United States.

Eli Lilly & Company has approximately 8,400 employees engaged in research and development. The company has manufacturing plants located in 13 countries and its products marketed in 143 countries.

ICOS is a Bothell, Washington-based Company that began operations in 1990. Many of the initial 65 staff members are still part of the approximately 675 people in the ICOS community. ICOS is dedicated to bringing novel and effective drugs to market that meet significant unmet medical needs, and can increase the quality of life for millions of people.

ICOS also manufactures protein-based materials used in clinical development for other pharmaceutical companies.

Lilly ICOS markets Tadalafil in North America and Europe, where it was initially launched.

The U.S. Food and Drug Administration approved Tadalafil in February 2003 as a treatment for Erectile Dysfunction.

Tadalafil was available in Europe for about a year before its FDA approval in 2003.

In order to debut the drug in the United States and cut into Viagra's overwhelming market presence, Lilly ICOS purchased several commercial spots during the broadcast of the 2004 Super Bowl.

Lilly ICOS has two other drug candidates undergoing clinical trials: tadalafil for treating enlargement of the prostate and IC485, a potential treatment for chronic obstructive pulmonary disease.

3.ABOUT Tadalafil MEDICATION

Tadalafil is a prescription medicine taken by mouth for the treatment of erectile dysfunction (ED) in men.

What is erectile dysfunction?

When a man can't get an erection to have sex or can't keep an erection long enough to finish having sex, it's called erectile dysfunction. Erectile dysfunction is also called impotence.

Is erectile dysfunction just a part of old age?

Erectile dysfunction doesn't have to be a part of getting older. It's true that as you get older, you may need more stimulation (such as stroking and touching) to get an erection. You might also need more time between erections. But older men should still be able to get an erection and enjoy sex.

What causes erectile dysfunction?

Medical problems that can cause erectile dysfunction:

• Diabetes (high blood sugar)
• Hypertension (high blood pressure)
• Atherosclerosis (hardening of the arteries)

If you can't keep your blood sugar or your blood pressure under control, you can get erectile dysfunction. It's important that you take your medicines for these problems just the way your doctor tells you.

Sometimes your hormones get out of balance and this causes erectile dysfunction. Your doctor will decide if you need blood tests to check your hormones.

Some medicines can cause this problem. If this is true for you, your doctor may take you off that medicine or give you a different one.

Drinking too much alcohol, smoking too much and abusing drugs can also cause erectile dysfunction.

Problems in your relationship with your sexual partner also can cause erectile dysfunction. You might try therapy to see if improving your relationship helps your sex life. Therapy will probably be most effective if your sex partner is included. Couples can learn new ways to please one another and to show affection. This can reduce any of your anxiety about having erections.

Physical causes of erectile dysfunction Alcoholism Fatigue Atherosclerosis (hardening of the arteries) Diabetes Brain or spinal-cord injuries Hypogonadism (which leads to lower testosterone levels) Liver or kidney failure Multiple sclerosis Parkinson's disease Radiation therapy to the testicles Stroke Some types of prostate or bladder surgery

Data source: The Impotence Resource Center, Boston University.

How is erectile dysfunction diagnosed?

Your doctor will probably start by asking you some questions and doing a physical exam. Samples of your blood and urine may be tested for diseases and disorders. Other tests may also be needed. Your doctor will determine which tests are right for you.

Feelings that can lead to erectile dysfunction

• Feeling nervous about sex, perhaps because of a bad experience or because of a previous episode of impotence
• Feeling stressed, including stress from work or family situations
• Being troubled by problems in your relationship with your sex partner
• Feeling depressed
• Feeling so self-conscious that you can't enjoy sex
• Thinking that your partner is reacting negatively to you

How erectile dysfunction is treated depends on what things are causing it. After your doctor checks you for medical problems and medicines that might cause erectile dysfunction, he or she may have you try a medicine like Tadalafil to help with erectile dysfunction. Tadalafil is taken by mouth.

Tadalafil is a member of a family of drugs known as PDE5 enzyme inhibitors.

Tadalafil is known as the " 36 hour pill" or the "weekend pill" because unlike other similar drugs, Tadalafil has a long duration of action.

Tadalafil blocks an enzyme that causes an erection to go flaccid. Although Tadalafil is similar to Levitra and Viagra, its dose, onset of action, and duration of action is unique.

However not everyone can use Tadalafil. Your doctor will help you decide if you can try Tadalafil.

What other options do you have?

If the medicines aren't right for you, you could also try using vacuum pump devices, or you could have surgery. Your doctor may send you to an urologist to talk about these options.

4.Tadalafil EFFECTIVENESS
When is Tadalafil best taken?

Tadalafil is taken orally. Tadalafil is available in 10 mg and 20 mg tablets.

Tadalafil works as fast as 16-30 minutes and can work up to 24-36 hours.

It has been observed through study that 595 of previously impotent men were able to have sex 36 hours after taking Tadalafil.

The recommended dose of Tadalafil is 10 mg taken prior to anticipated sexual activity and without regard to food. In those patients in whom Tadalafil 10 mg does not produce an adequate effect, 20 mg might be tried. Tadalafil can be taken from 30 minutes to 12 hours prior to sexual activity. The efficacy of Tadalafil may persist up to 24 hours post-dose.

Tadalafil is readily absorbed from the bloodstream following oral administration. 16% of the total drug is available for activity. Tadalafil is about 94% bound to plasma protein. Maximum plasma concentration of Tadalafil was achieved 2 hours post dose. The Tadalafil label states that It can be taken from 30 minutes to 12 hours prior to sexual activity. Efficacy of Tadalafil may persist up to 24 hours post-dose.

Tadalafil is broken down in the liver by an enzyme known as CYP3A4 and to a lesser extent CYPC2. Tadalafil breakdown products are excreted in the feces (61%) and in the urine (36%).

17.5 hours are required for the quantity of Tadalafil in the body to be reduced to half of its original level through various elimination processes in a healthy man.

5.Tadalafil EFFECTS ON SPECIAL POPULATION
How do different people react to Tadalafil?

•  Geriatric - Healthy male elderly subjects (65 years or over) have a lower oral clearance of Tadalafil, resulting in 25% higher exposure of Tadalafil relative to that observed in healthy subjects 19 to 45 years of age. No dose adjustment is warranted based on age alone. However, greater sensitivity to medications in some older individuals should be considered.

•  Pediatric - Tadalafil has not been evaluated in individuals less than 18 years old.

6.Tadalafil EFFECTS ON MEDICAL CONDITIONS
How does Tadalafil affect your existing condition/ailment?

•  Hepatic Impairment - In clinical pharmacology studies, Tadalafil exposure in subjects with mild or moderate hepatic impairment was comparable to exposure in healthy subjects when a dose of 10 mg was administered. There are no available data for doses higher than 10 mg of Tadalafil in patients with hepatic impairment. Insufficient data are available for subjects with severe hepatic impairment. Therefore, for patients with mild or moderate hepatic impairment, the maximum dose should not exceed 10 mg, and use in patients with severe hepatic impairment is not recommended.

•  Renal Insufficiency- In patients on hemodialysis taking 10-or 20-mg Tadalafil (tadalafil), there were no reported cases of back pain. The dose of Tadalafil, tadalafil should be limited to 5 mg not more than once daily in patients with severe renal insufficiency or end-stage renal disease. A starting dose of Tadalafil 5 mg not more than once daily is recommended for patients with moderate renal insufficiency; the maximum recommended dose of Tadalafil is 10 mg not more than once in every 48 hours. No dose adjustment is required in patients with mild renal insufficiency.

•  Diabetes Mellitus- In male patients with diabetes mellitus after a 10 mg Tadalafil (tadalafil) dose, exposure to the drug was reduced approximately 19% and maximum concentration was 5% lower than that observed in healthy subjects. No dose adjustment is warranted.

•  Effects on Blood Pressure-Tadalafil 20 mg administered to healthy male subjects produced no significant difference compared to placebo in supine systolic and diastolic blood pressure (difference in the mean maximal decrease of 1.6/ 0.8 mm Hg, respectively) and in standing systolic and diastolic blood pressure (difference in the mean maximal decrease of 0.2/ 4.6 mm Hg, respectively). In addition, there was no significant effect on heart rate.

•  Effects on Sperm Characteristics- There were no clinically relevant effects on sperm concentration, sperm count, motility, or morphology in humans in placebo-controlled studies of daily doses of Tadalafil 10 mg or 20 mg for 6 months. In addition, Tadalafil had no effect on serum levels of testosterone, luteinizing hormone, or follicle stimulating hormone.

7.OTHER/ALTERNATE USES OF Tadalafil
What else does Tadalafil treat?

Tadalafil is undergoing Phase II Clinical trials for sexual dysfunction in women.

8.ADVERSE/SIDE EFFECTS of Tadalafil
What are the side effects of Tadalafil

Tadalafil was administered to over 5700 men (mean age 59, range 19 to 87 years) during clinical trials worldwide. Over 1000 patients were treated for 1 year or longer and over 1300 patients were treated for 6 months or more.

In placebo-controlled Phase 3 clinical trials (A placebo is a medical treatment (operation, therapy, chemical solution, pill, etc.), which is administered as if it were a therapy, but which has no therapeutic value other than the placebo effect), the discontinuation rate due to adverse events in patients treated with Tadalafil 10 or 20 mg was 3.1%, compared to 1.4% in placebo-treated patients. When Tadalafil was taken as recommended in the placebo-controlled clinical trials, the following adverse events were reported (see Table below):

Back pain or myalgia was reported at incidence rates described in Table 7. In Tadalafil clinical pharmacology trials, back pain or myalgia generally occurred 12 to 24 hours after dosing and typically resolved within 48 hours. The back pain/ myalgia associated with Tadalafil treatment was characterized by diffuse bilateral lower lumbar, gluteal, thigh, or thoracolumbar muscular discomfort.

Overall, approximately 0.5% of all tadalafil-treated subjects discontinued treatment as a consequence of back pain/ myalgia. Diagnostic testing, including measures for inflammation, muscle injury, or renal damage revealed no evidence of medically significant underlying pathology.

Across all studies with any Tadalafil dose, reports of changes in color vision were rare (< 0.1% of patients).

The other adverse effects include

• an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);
• chest pain or irregular heartbeats;
• dizziness, nausea, or angina (pain, tightness, discomfort, numbness, or tingling in the chest, arms, neck, or jaw);
• swelling of the ankles or legs;
• shortness of breath;
• prolonged or severe dizziness; or
• a prolonged (lasting longer than 4 hours) or painful erection.
• headache;
• indigestion;
• stuffy or runny nose; or
• temporary blue tint in vision or difficulty telling the difference between the colors blue and green (uncommon).

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

9. USEFUL SITES

Newer Pharmacologic Alternatives for Erectile Dysfunction

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