Tadalafil for erectile dysfunction

Clinical bottom line
Both 10 mg and 20 mg of tadalafil were significantly better than placebo in producing erections hard enough for penetration, hard enough for penetration and of long enough duration for successful intercourse, and provided improved erections. Numbers needed to treat for improved erections were 2.6 for tadalafil 10 mg and 2.0 for tadalafil 20 mg.

Reference
CC Carson et al. The efficacy and safety of tadalafil: an update. BJU International 2004 93: 1276-1281

Background
Though a number of systematic reviews of sildenafil have been published in the years before 2004, systematic reviews and meta-analyses of the newer oral erectile dysfunction drugs in the same class (phosphodiesterase type 5 inhibitor) have not been until 2004. This at least opens the possibility of comparing and contrasting different treatments based on similar trials with similar outcomes.

Systematic review
The review calls itself an integrated review. There is no search strategy, and the assumption is that the data comes from studies conducted by Eli Lilly, as one of the authors is an employee. No non-company studies are therefore likely. It is not certain whether the data come from clinical trial reports, or databases.

Date review completed: Last study completed in February 2003.
Number of trials included: 11 multicentre trials with tadalafil 10 mg (321 men) and 20 mg (1143 men).
Number of patients: 2102
Control groups: placebo
Main outcomes: International Index of Erectile Function (IIEF), plus other scales. Main responses were erection hard enough for penetration, and hard enough for penetration lasting long enough for successful intercourse.
Patients in the trials were required to make at least four attempts at intercourse during a four-week treatment-free period. They were then randomised to 12 weeks of treatment with placebo, or tadalafil 10 or 20 mg. Treatment was taken as needed before sexual intercourse, without restrictions on food or timing of sexual activity.

Men had to be 18 years old or older, with a minimum three-month history of mild to severe erectile dysfunction of organic, psychogenic, or mixed causes. They had to have a steady female partner. Most studies excluded non-responders to previous sildenafil treatment.

Results
There were 2,102 men in the trials, with an average age of 56 years. And 22% over age 65 years. Most had a history of erectile dysfunction of over a year. Medical history of hypertension (29%), diabetes (20%), hyperlipidaemia (16%) coronary artery disease (5% and depression (4%) were common. Severity of erectile dysfunction was mild in 36%, moderate in 27% and severe in 33%.

Completion rates in trials was high (89%), with adverse event discontinuation (3.2%) or lack of efficacy discontinuation (1.6%) uncommon. Analyses were by intention to treat, using a definition of all patients measured at baseline with at least one later measurement, which means that men had to complete four weeks.

Efficacy
Both 10 mg and 20 mg were significantly better than placebo in producing erections hard enough for penetration, hard enough for penetration and of long enough duration for successful intercourse, and provided improved erections (Table 1). Numbers needed to treat for improved erections were 2.6 for tadalafil 10 mg and 2.0 for tadalafil 20 mg.

Source from: jr2.ox.ac.uk

Cialis (tadalafil)

FDA ALERT [07/2005]: A small number of men have lost eyesight in one eye some time after taking Cialis, Viagra, or Levitra. This type of vision loss is called non-arteritic anterior ischemic optic neuropathy (NAION). NAION causes a sudden loss of eyesight because blood flow is blocked to the optic nerve.

We do not know at this time if Cialis, Viagra or Levitra causes NAION. NAION also happens in men who do not take these medicines. People who have a higher chance for NAION include those who:

have heart disease
are over 50 years old
have diabetes
have high blood pressure
have high cholesterol
smoke
have certain eye problems
FDA has approved new labels for Cialis, Viagra, and Levitra to include information on possible eyesight loss (NAION).
Stop using Cialis, Viagra, or Levitra if you have a loss in your eyesight. Get medical help right away.
Current Information

Patient Information Sheet [PDF] [HTML]
Healthcare Professional Sheet [PDF] [HTML]
FDA Statement
Label (7/8/2005)

Source from: fda.gov

Pharmacy Author: Omudhome Ogbru, Pharm.D.
Medical Editor: Jay Marks, M.D.

GENERIC NAME: tadalafil

BRAND NAME: Cialis
DRUG CLASS AND MECHANISM: Tadalafil is an oral drug that is used to treat impotence (the inability to attain or maintain a penile erection.). It is a phosphodiesterase inhibitor that is similar to sildenafil (Viagra) and vardenafil (Levitra).

Penile erection is caused by the engorgement of the penis with blood. This engorgement occurs when the blood vessels delivering blood to the penis increase in size and increase the delivery of blood to the penis. At the same time, the blood vessels carrying blood away from the penis decrease in size and decrease the removal of blood from the penis. Sexual stimulation that leads to the engorgement and erection causes the production and release of nitric oxide in the penis. Nitric oxide then activates the enzyme, guanylate cyclase to produce cyclic guanosine monophosphate (cGMP). The cGMP is primarily responsible for increasing and decreasing the size of the blood vessels carrying blood to and from the penis, respectively. Tadalafil prevents an enzyme called phosphodiesterase-5 from destroying cGMP so that cGMP persists longer. The longer cGMP persists, the more prolonged the engorgement of the penis. Tadalafil was approved by the FDA in November, 2003.

PRESCRIPTION: Yes.

GENERIC AVAILABLE: No.

PREPARATIONS: Tablets: 5, 10, and 20 mg.

STORAGE: Store at room temperature between 15-30癈 (59-86癋).

PRESCRIBED FOR: Tadalafil is used for the treatment of impotence.

DOSING: For most individuals, the recommended starting dose of tadalafil is 10 mg per day taken before sexual activity. Depending on the adequacy of the response or side effects, the dose may be increased to 20 mg or decreased to 5 mg a day. The effect of tadalafil may last up to 36 hours. Individuals who are taking medications that increase the blood levels of tadalafil should not exceed 10 mg in 72 hours (See drug interactions.)

DRUG INTERACTIONS: The breakdown and elimination of tadalafil from the body may be decreased by erythromycin, ketoconazole (Nizoral), itraconazole (Sporanox), indinavir (Crixivan) and ritonavir (Norvir). Therefore, these drugs may increase the concentration of tadalafil in the blood. If these drugs are being used at the same time as tadalafil, the dose of tadalafil should be reduced in order to avoid side effects from high levels of tadalafil. Tadalafil increases the heart rate and also exaggerates the blood pressure lowering effects of nitrates (e.g., nitroglycerin). In patients who take nitrates for chest pain (angina), tadalafil could cause chest pain by increasing heart rate and lowering blood pressure. Therefore, patients with angina should not use tadalafil. Tadalafil also exaggerates the blood pressure lowering effects of some alpha-blocking drugs e.g., terazosin (Hytrin). Individuals who take these alpha-blockers should not use tadalafil.

PREGNANCY: Tadalafil is not approved for use in pregnant women.

NURSING MOTHERS: Tadalafil has not been evaluated in women who are breastfeeding.

SIDE EFFECTS: The most common side effects of tadalafil are facial flushing (reddening), headaches, stomach upset, diarrhea, flu-like symptoms and nausea. Tadalafil also may cause chest pain, low blood pressure, blurred vision and changes in color vision, abnormal ejaculation and priapism (prolonged and painful erection).

Source from: medicinenet.com

Tadalafil Drug Information

Generic Name: tadalafil (tah DAL a fil)
Brand Names: Cialis

What is the most important information I should know about tadalafil?
Do not take tadalafil if you are taking any of the following medicines:

• a nitrate such as nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, Minitran, Deponit, Transderm-Nitro, others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), isosorbide mononitrate (Imdur, ISMO, Monoket), and others;
• nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers"); or
• an alpha blocker (other than tamsulosin (Flomax) 0.4 mg once a day) such as doxazosin (Cardura), guanadrel (Hylorel), prazosin

(Minipress), terazosin (Hytrin), alfuzosin (Uroxatral), and others.
Taking tadalafil with any of these medications may cause very low blood pressure, possibly resulting in dizziness, fainting, stroke, or heart attack.

Contact your doctor or seek emergency medical attention for any erection that lasts longer than 4 hours. A sustained erection can damage the penis.

Refrain from further sexual activity and notify your doctor it you develop dizziness, nausea, or angina (pain, tightness, discomfort, numbness, or tingling in the chest, arms, neck, or jaw) during sexual activity.
Tadalafil is usually taken when needed before sexual activity. The effects of tadalafil may last for up to 36 hours or more. Your doctor will determine how often you can take tadalafil. Do not take tadalafil more often than is directed by your doctor.

What is tadalafil?

• Tadalafil relaxes muscles within the penis. This allows increased blood flow into the penis, necessary to achieve and maintain an erection.
• Tadalafil is used to treat erectile dysfunction (impotence).
• Tadalafil may also be used for purposes other than those listed in this medication guide.

What should I discuss with my healthcare provider before taking tadalafil?
Do not take tadalafil if you are taking any of the following medicines:

• a nitrate such as nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, Minitran, Deponit, Transderm-Nitro, others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), isosorbide mononitrate (Imdur, ISMO, Monoket), and others;
• nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers"); or
• an alpha blocker (other than tamsulosin (Flomax) 0.4 mg once a day) such as doxazosin (Cardura), guanadrel (Hylorel), prazosin (Minipress), terazosin (Hytrin), alfuzosin (Uroxatral), and others.

Taking tadalafil with any of these medications may cause very low blood pressure, possibly resulting in dizziness, fainting, stroke, or heart attack.

Before taking tadalafil, tell your doctor if you

• have heart problems such as angina, heart failure, irregular heartbeats, or have had a heart attack;
• have low blood pressure or high blood pressure that is not controlled;
• have had a stroke;
• have liver problems;
• have kidney problems;
• have ever had blood cell problems such as sickle cell anemia, multiple myeloma, or leukemia;
• have a bleeding disorder;
• have a stomach ulcer;
• have retinitis pigmentosa (an inherited condition of the eye);
• have a physical deformity of the penis such as Peyronie's disease;
• had an erection that lasted longer than 4 hours.

You may not be able to take tadalafil, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Although tadalafil is not indicated for use by women, it is in the FDA pregnancy category B. This means that tadalafil is not expected to be harmful to an unborn baby. Tadalafil should not be taken by women.

It is not known whether tadalafil passes into breast milk. Tadalafil should not be taken by women.
If you are over 65 years of age, you may be more likely to experience side effects from tadalafil. Your doctor may prescribe a lower dose of this medication.

Source from: drugs.com

Tadalafil for erectile dysfunction

Synopsis

Tadalafil is a reversible phosphodiesterase type 5 (PDE5) inhibitor approved for the treatment of erectile dysfunction (ED). As a class, PDE5 inhibitors (including sildenafil [Viagra] and vardenafil [Levitra]), enhance erectile response to sexual stimulation by increasing penile blood flow. The duration of action of tadalafil is longer than that of sildenafil or vardenafil.

Safety

In general, few side effects occur with tadalafil unless it is taken in conjunction with other drugs. When combined with [[alpha].sub.1]-adrenergic blockers such as doxazosin (Cardura), prazosin (Minipress), and terazosin (Hytrin) but not tamsulosin (Flomax)--tadalafil can cause a significant drop in blood pressure. Similarly, concomitant use of nitrates (including recreational nitrates known as "poppers") with tadalafil also is contraindicated. For life-threatening situations, nitrates may be considered if at least 48 hours have passed since the last dose of tadalafil and if close hemodynamic monitoring is available. Tadalafil will lower blood pressure an additional 4 to 10 mm Hg when used with antihypertensive drugs. Dosage should be limited to 10 mg within a 72-hour period when patients are also taking drugs such as erythromycin, ketoconazole (Nizoral), itraconazole (Sporanox), protease inhibitors, and other drugs that inhibit the CYP3A4 enzyme system. (1)

Patients with cardiovascular diseases have been excluded from studies of tadalafil because so little is known about its safety profile in this population. (1) The current recommendation for patients who experience coital angina after taking a PDE5 inhibitor is to contact emergency services that provide transport to a hospital. (2) Rare reports of priapism have been reported with all of the drugs in this class. (1) Long-term safety has not been established. Because of tadalafil's long duration of action, patients are exposed to its effects for a longer period of time than with sildenafil or vardenafil. (3,4)

Tolerability

The most common dose-related side effects of tadalafil are headache (11 to 15 percent) and dyspepsia (8 to 10 percent). Back pain, beginning 12 to 24 hours after the dose and lasting for up to 48 hours, was reported in 5 to 6 percent of men, as compared with a rate of 3 percent in men receiving placebo. Changes in color vision, which has been reported with sildenafil, has been reported in less than 0.1 percent of patients in clinical trials of tadalafil. (1) Tadalafil differs from sildenafil in its affinity for PDE6 and 11, which may account for fewer reported ocular effects and more reports of back pain with tadalafil than with sildenafil. (3)

Effectiveness

The main outcomes studied in the treatment of ED are achievement of an erection, successful intercourse, and overall satisfaction with sexual function. In five studies evaluating tadalafil in 5-, 10-, and 20-mg doses versus placebo, 321 men were assigned to a 10-mg regimen. In this group, 68 to 77 percent of men reported an erection suitable for insertion, compared with 42 to 55 percent receiving placebo (number needed to treat [NNT]=4 to 4.5). However, slightly fewer men reported successful intercourse (51 to 70 percent, NNT=4 to 5). (1,5) The satisfaction with intercourse was 9.3 out of a maximum score of 15, compared with a score of 7.4 in patients taking placebo, and overall satisfaction was 6.7 out of a possible 10 with tadalafil compared with 5.2 in patients taking placebo. (5) As with the other drugs in this class, overall effectiveness is diminished in patients with diabetes or ED. Tadalafil has not been studied in patients with antidepressant-induced ED. No studies have directly compared tadalaf il with sildenafil or vardenafil, but overall success rates have been comparable among the three options.

Source from: findarticles.com

TADALAFIL

BRAND NAME: CIALIS

Manufacturing Details
Our Tadalafil is produced in Indian FDA and GMP compliant plants. Some of the plants are American FDA approved.

Description
Tadalafil is used to treat men who have erectile dysfunction (also called sexual impotence). Like Sildenafil Citrate, it's very easy to use, however this pill is more effective and has less side effects.

Because it is s a more effective product, Tadalafil starts working up to twice as fast as Sildenafil Citrate, and continues working for up to 24-36 hours, compared to Sildenafil Citrate's 4-6 hour effective life. It is taken about half an hour before any sexual activity begins. It also works for more people; In tests Sildenafil Citrate was found to work for 65% of people that tried it. Under the same tests Tadalafil was found to work for 82% of people that tried it. And the unpleasant side effects? Very few people have reported experiencing side effects.

Cialis ( Tadalafil ) Lilly/ICOS

Dec 1, 2003
Formulary

Tadalafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). The drug is approved for the treatment of erectile dysfunction.

Efficacy. 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 was taken (20 mg QD) by patients enrolled from the general erectile dysfunction (ED) population. 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 the Sexual Encounter Profile. The IIEF EF domain consists of a 30-point score, where higher scores indicate better erectile function. For the EF domain score outcome in Study A, the tadalafil group demonstrated a 6.9-point change from baseline compared to a ­0.2-point change from baseline in the placebo group (P<.001). In Study B, the point changes from baseline were 9.3 and 0.3 in the tadalafil and placebo groups, respectively (P<.001). 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.

Safety. Tadalafil potentiates the hypotensive effect of nitrates; therefore, tadalafil administration is contraindicated in patients taking any form of nitrates. Administration of tadalafil in patients taking any a-adrenergic antagonist other than 0.4 mg QD tamsulosin is contraindicated. Patients with left ventricular outflow obstruction may be sensitive to the action of vasodilators, including PDE5 inhibitors such as tadalafil . The most common adverse events reported with tadalafil are headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and limb pain. There have been rare reports of prolonged erections (duration >4 h) and priapism with drugs belonging to the same class as tadalafil .

Dosing. Tadalafil should be dosed at 10 mg in most patients, to be taken prior to anticipated sexual activity. This dose may be increased to 20 mg or decreased to 5 mg based on individual efficacy and tolerability. The maximum dosing frequency is once per day. In patients with moderate renal insufficiency the maximum dose should not exceed 10 mg every 48 hours. In patients with severe renal insufficiency on hemodialysis, the maximum recommended dose is 5 mg not more than once every 48 hours. In patients with mild or moderate degrees of hepatic impairment, the dose of tadalafil should not exceed 10 mg once daily, and tadalafil is not recommended in patients with severe hepatic impairment. In patients taking concomitant potent inhibitors of CYP3A4 (eg, ketoconazole or ritonavir) the recommended dose of tadalafil is 10 mg, not to exceed once every 72 hours. [ To view the website and learn more info ]

Tadalafil (Cialis)

Tadalafil is a phosphodiesterase 5 inhibitor developed for the treatment of male erectile disfunction (ED) resulting from organic or mixed organic-psychogenic origin.

MOA: Tadalafil is an inhibitor of the enzyme phosphodiesterase (PDE) showing a higher degree of specificity for PDE5 than that reported for sildenafil or vardenafil. Inhibition of PDE5 hydrolysis results in prolonged erection (See sildenafil for more details). Tadalafil is reported to inhibit PDE5 780-fold greater than PDE6 and 9,000-fold greater than PDE1-4 and PDE7-10. The selectivity of tadalafil for PDE11 is only 5-fold greater than for PDE5, but the clinical significance of PDE11 is not presently known.

Metabolism: Tadalafil is metabolized by CYP3A4 resulting in formation methylcatechol glucuronide, which is inactive.

References:
Curran MP, Keating GM. Tadalafil. Drugs 2003; 63:2203-2212.
Daugan A, Grondin P, Ruault C, et al. The discovery of tadalafil: A novel and highly selective PDE5 inhibitor. 1: 5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione analogues. J Med Chem 2003; 46:4525-4532.
Daugan A, Grondin P, Ruault C, et al. The discovery of tadalafil: A novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogue. J Med Chem 2003; 46:4533-4542.
Maw GN, Allerton CMN, Gbekor E, et al. Design, synthesis and biological activity of ?-carboline-based type-5 phosphodiesterase inhibitors. Bioorgan & Med Chem Letters 2003; 13:1425-1428.
Padma-Nathan H. Efficacy and tolerability of tadalafil, a novel phosphodiesterase 5 inhibitor, in treatment of erectile dysfunction. Am J Card 2003; 92:19M-25M.

Tadalafil For Erectile Dysfunction, Cialis, Tadalafil Drug Information, Tadalafil For Erectile Dysfunction And More Tadalafil Resources.

Third ED drug approved: introducing Cialis

Diabetes Forecast , June, 2004 by Shauna S. Roberts

IN NOVEMBER 2003, the Food and Drug Administration approved tadalafil (Cialis) for erectile dysfunction (ED, impotence). It is the third ED drug in pill form, Sildenafil (Viagra) became available in 1998 and vardenafil (Levitra), in August 2003.

Tadalafil lasts longer in the body than the other two drugs. It can improve the ability to have sex for as long as 36 hours. Unlike the other ED drugs, whose dosing instructions say to take them one hour before sex, tadalafil's instructions do not give a time. Instead, you should discuss with your doctor when you should take tadalafil . In studies, some men were able to have sex within half an hour of taking the drug. It should not be used more than once a day.

Tadalafil's warnings, drug interactions, and side effects are similar to those of sildenafil and vardenafil. (See "Levitra, A New Option For ED," Diabetes Forecast, March 2004, pages 30-31.) The most common side effects are headache, indigestion, back pain, muscle aches, flushing, and stuffy or runny nose. Drinking large amounts of alcohol (five glasses of wine, for instance) can worsen side effects, sometimes dangerously so.

Tadalafil is not suitable for everyone. Thus, as with the other ED pills, it's vital to discuss with your doctor whether tadalafil is right for you and what dose is appropriate. Click here for more related articles ......