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This page contains drug information on Cialis.
The information provided includes the following:
1)what is Cialis
2)the possible side effects of Cialis
3)what happens if you miss a dose of Cialis
4)what happens if you overdose with Cialis
5)the most important information about Cialis
6)how to use Cialis
7)other drugs that may affect Cialis
8)what to avoid while using Cialis


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



What is the most important information I should know about Cialis(Tadalafil)?




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Do not take Cialis(Tadalafil) if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, and others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers"). Taking tadalafil with a nitrate medicine can cause a serious decrease in blood pressure, leading to fainting, stroke, or heart attack.

If you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw during sexual activity, stop and call your doctor right away. You could be having a serious side effect of tadalafil.

Do not take Cialis(Tadalafil) more than once a day. Allow 24 hours to pass between doses.

Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis.

A small number of patients have had a sudden loss of eyesight after taking Cialis(Tadalafil). This type of vision loss is caused by decreased blood flow to the optic nerve of the eye. It is not clear whether Cialis(Tadalafil) is the actual cause of such vision loss. Sudden vision loss with Cialis(Tadalafil) use has occurred most often in people with heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoke or are over 50 years old.

Stop using tadalafil and get emergency medical help if you have sudden vision loss.

What is Cialis(Tadalafil)?




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Cialis(Tadalafil) relaxes muscles and increases blood flow to particular areas of the body.

Cialis(Tadalafil) is used to treat erectile dysfunction (impotence).

Cialis(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 Cialis(Tadalafil)?


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Do not take Cialis(Tadalafil) if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, and others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers"). Taking Cialis(Tadalafil) with a nitrate medicine can cause a serious decrease in blood pressure, leading to fainting, stroke, or heart attack.

A small number of patients have had a sudden loss of eyesight after taking Cialis(Tadalafil). This type of vision loss is caused by decreased blood flow to the optic nerve of the eye. It is not clear whether Cialis(Tadalafil) is the actual cause of such vision loss. Sudden vision loss with Cialis(Tadalafil) use has occurred most often in people with heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoke or are over 50 years old.

Before taking Cialis(Tadalafil), tell your doctor if you have:
·
heart disease or heart rhythm problems;
·
a recent history a heart attack (within the past 90 days);
·
a recent history of stroke or congestive heart failure (within the past 6 months);
·
angina (chest pain);
·
high or low blood pressure;
·
liver disease;
·
kidney disease (or if you are on dialysis);
·
a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;
·
a bleeding disorder such as hemophilia;
·
a stomach ulcer;
·
retinitis pigmentosa (an inherited condition of the eye);
·
a physical deformity of the penis (such as Peyronie's disease); or
·
if you have been told you should not have sexual intercourse for health reasons.

If you have any of these conditions, you may not be able to use Cialis(Tadalafil) or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category B: Although Cialis(Tadalafil) is not for use in women, this medication is not expected to be harmful to an unborn baby. Do not use Cialis(Tadalafil) without telling your doctor if you are pregnant or plan to become pregnant during treatment.

Although Cialis(Tadalafil) is not for use in women, it is not known if Cialis(Tadalafil) passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

You may need a lower dose of this medication if you are older than 65. Follow your doctor's instructions.

How should I take Cialis(Tadalafil)?




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Take Cialis(Tadalafil) exactly as it was prescribed for you. Do not take it in larger doses or for longer than recommended by your doctor.

Take each dose with a full glass of water.

Cialis(Tadalafil) can be taken with or without food.

Cialis(Tadalafil) is usually taken only when needed, just before sexual activity. The medication can help achieve an erection when sexual stimulation occurs. An erection will not occur just by taking a pill. Follow your doctor's instructions.

Do not take Cialis(Tadalafil) more than once a day. Allow 24 hours to pass between doses.

Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis.

Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?




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Since Cialis(Tadalafil) is used as needed, you are not likely to be on a dosing schedule.

What happens if I overdose?




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Seek emergency medical attention if you think you have used too much of this medicine.

Symptoms of a Cialis(Tadalafil) overdose may include chest pain, nausea, irregular heartbeat, and feeling light-headed or fainting.

What should I avoid while taking Cialis(Tadalafil)?




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Avoid drinking alcohol, which can increase some of the side effects of Cialis(Tadalafil).

Grapefruit and grapefruit juice may interact with tadalafil. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Do not use any other drug to treat impotence, such as alprostadil (Caverject, Muse, Edex) or yohimbine (Yocon, Yodoxin, others), unless your doctor tells you to.

What are the possible side effects of Cialis(Tadalafil)?




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If you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw during sexual activity, stop and call your doctor right away. You could be having a serious side effect of Cialis(Tadalafil).

Stop using Cialis(Tadalafil) and get emergency medical help if you have sudden vision loss.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using tadalafil and call your doctor at once if you have any of these serious side effects:
·
chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
·
irregular heartbeat;
·
swelling in your hands, ankles, or feet;
·
shortness of breath;
·
vision changes;
·
feeling light-headed, fainting; or
·
penis erection that is painful or lasts 4 hours or longer.

Continue taking tadalafil and talk with your doctor if you have any of these less serious side effects:
·
warmth or redness in your face, neck, or chest;
·
stuffy nose;
·
headache;
·
upset stomach; or
·
back pain.

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.
What other drugs will affect Cialis(Tadalafil)?

Before taking tadalafil, tell your doctor if you are using any of the following medications:
·
cimetidine (Tagamet, Tagamet HB);
·
erythromycin (E-Mycin, Eryc, Ery-Tab) or clarithromycin (Biaxin);
·
doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin);
·
HIV medicines such as amprenavir (Agenerase), tipranavir (Aptivus), darunavir (Prezista), efavirenz (Sustiva), nevirapine (Viramune), indinavir (Crixivan), saquinavir (Invirase, Fortovase), lopinavir/ ritonavir (Kaletra), fosamprenavir (Lexiva), ritonavir (Norvir), atazanavir (Reyataz), or nelfinavir (Viracept);
·
itraconazole (Sporanox) or ketoconazole (Nizoral);
·
carbamazepine (Tegretol), phenobarbital (Luminal), or phenytoin (Dilantin); or
·
rifampin (Rifadin, Rimactane).

If you are using any of these drugs, you may not be able to take Cialis(Tadalafil), or you may need dosage adjustments or special tests during treatment.

There may be other drugs not listed that can affect Cialis(Tadalafil). Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?




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Your pharmacist has additional information about tadalafil written for health professionals that you may read.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/ or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.


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CIALISÒ(tadalafil) tablets

CIALISÒ(tadalafil) tablets DESCRIPTION CIALISÒ (tadalafil), an oral treatment for erectile dysfunction, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Tadalafil has the empirical formula C22H19N3O4 representing a molecular weight of 389.41. The structural formula is: The chemical designation is pyrazino[1ґ,2ґ:1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-. It is a crystalline solid that is practically insoluble in water and very slightly soluble in ethanol. CIALIS is available as film-coated, almond-shaped tablets for oral administration. Each tablet contains 5, 10, or 20 mg of tadalafil and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, hypromellose, iron oxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, talc, titanium dioxide, and triacetin.

CLINICAL PHARMACOLOGY Cialis(Tadalafil)

CLINICAL PHARMACOLOGY Cialis(Tadalafil) Mechanism of Action Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Cialis(Tadalafil) inhibits PDE5. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by Cialis(Tadalafil) has no effect in the absence of sexual stimulation. Studies in vitro have demonstrated that Cialis(Tadalafil) is a selective inhibitor of PDE5. PDE5 is found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas. In vitro studies have shown that the effect of Cialis(Tadalafil) is more potent on PDE5 than on other phosphodiesterases. These studies have shown that Cialis(Tadalafil) is >10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Cialis(Tadalafil) is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, Cialis(Tadalafil) is 700-fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. Cialis(Tadalafil) is >9,000-fold more potent for PDE5 than for PDE8, PDE9, and PDE10 and 14-fold more potent for PDE5 than for PDE11A1, an enzyme found in human skeletal muscle. Cialis(Tadalafil) inhibits human recombinant PDE11A1 activity at concentrations within the therapeutic range. The physiological role and clinical consequence of PDE11 inhibition in humans have not been defined. Pharmacokinetics Over a dose range of 2.5 to 20 mg, Cialis(Tadalafil) exposure (AUC) increases proportionally with dose in healthy subjects. Steady-state plasma concentrations are attained within 5 days of once-daily dosing, and exposure is approximately 1.6-fold greater than after a single dose. Cialis(Tadalafil) is eliminated predominantly by hepatic metabolism, mainly by cytochrome P450 3A4 (CYP3A4). The concomitant use of potent CYP3A4 inhibitors such as ritonavir or ketoconazole resulted in significant increases in Cialis(Tadalafil) AUC values (see PRECAUTIONS and DOSAGE AND ADMINISTRATION). Mean Cialis(Tadalafil) concentrations measured after the administration of a single oral dose of 20 mg to healthy male subjects are depicted in Figure 1. Figure 1: Plasma Cialis(Tadalafil) concentrations (mean ± SD) following a single 20-mg Cialis(Tadalafil) dose Absorption — After single oral-dose administration, the maximum observed plasma concentration (Cmax) of Cialis(Tadalafil) is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of Cialis(Tadalafil) following oral dosing has not been determined. The rate and extent of absorption of Cialis(Tadalafil) are not influenced by food; thus CIALIS may be taken with or without food. Distribution — The mean apparent volume of distribution following oral administration is approximately 63 L, indicating that Cialis(Tadalafil) is distributed into tissues. At therapeutic concentrations, 94% of Cialis(Tadalafil) in plasma is bound to proteins. Less than 0.0005% of the administered dose appeared in the semen of healthy subjects. Metabolism — Cialis(Tadalafil) is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. The major circulating metabolite is the methylcatechol glucuronide. Methylcatechol concentrations are less than 10% of glucuronide concentrations. In vitro data suggests that metabolites are not expected to be pharmacologically active at observed metabolite concentrations. Elimination — The mean oral clearance for Cialis(Tadalafil) is 2.5 L/hr and the mean terminal half-life is 17.5 hours in healthy subjects. Cialis(Tadalafil) is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose). Pharmacokinetics in Special Populations Geriatric — Healthy male elderly subjects (65 years or over) had a lower oral clearance of Cialis(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. No dose adjustment is warranted based on age alone. However, greater sensitivity to medications in some older individuals should be considered (see Geriatric Use under PRECAUTIONS). Pediatric — Cialis(Tadalafil) has not been evaluated in individuals less than 18 years old. Hepatic Impairment — In clinical pharmacology studies, Cialis(Tadalafil) exposure (AUC) in subjects with mild or moderate hepatic impairment (Child-Pugh Class A or B) 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 Cialis(Tadalafil) in patients with hepatic impairment. Insufficient data are available for subjects with severe hepatic impairment (Child-Pugh Class C). 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 (see DOSAGE AND ADMINISTRATION). Renal Insufficiency — In clinical pharmacology studies using single-dose Cialis(Tadalafil) (5 to 10 mg), Cialis(Tadalafil) exposure (AUC) doubled in subjects with mild (creatinine clearance 51 to 80 mL/min) or moderate (creatinine clearance 31 to 50 mL/min) renal insufficiency. In subjects with end-stage renal disease on hemodialysis, there was a two-fold increase in Cmax and 2.7- to 4.1-fold increase in AUC following single-dose administration of 10 or 20 mg Cialis(Tadalafil). Exposure to total methylcatechol (unconjugated plus glucuronide) was 2- to 4-fold higher in subjects with renal impairment, compared to those with normal renal function. Hemodialysis (performed between 24 and 30 hours post-dose) contributed negligibly to Cialis(Tadalafil) or metabolite elimination. In a clinical pharmacology study (N=28) at a dose of 10 mg, back pain was reported as a limiting adverse event in male patients with moderate renal impairment. At a dose of 5 mg, the incidence and severity of back pain was not significantly different than in the general population. In patients on hemodialysis taking 10- or 20-mg Cialis(Tadalafil), there were no reported cases of back pain. The dose of Cialis(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 5 mg not more than once daily is recommended for patients with moderate renal insufficiency; the maximum recommended dose is 10 mg not more than once in every 48 hours. No dose adjustment is required in patients with mild renal insufficiency (see DOSAGE AND ADMINISTRATION). Patients with Diabetes Mellitus — In male patients with diabetes mellitus after a 10 mg Cialis(Tadalafil) dose, exposure (AUC) was reduced approximately 19% and Cmax was 5% lower than that observed in healthy subjects. No dose adjustment is warranted. Pharmacodynamics Effects on Blood Pressure — Cialis(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 Blood Pressure when CIALIS is Administered with Nitrates — In clinical pharmacology studies, Cialis(Tadalafil) (5 to 20 mg) was shown to potentiate the hypotensive effect of nitrates. Therefore, the use of CIALIS in patients taking any form of nitrates is contraindicated (see CONTRAINDICATIONS). A study was conducted to assess the degree of interaction between nitroglycerin and Cialis(Tadalafil), should nitroglycerin be required in an emergency situation after Cialis(Tadalafil) was taken. This was a double-blind, placebo-controlled, crossover study in 150 male subjects at least 40 years of age (including subjects with diabetes mellitus and/or controlled hypertension) and receiving daily doses of Cialis(Tadalafil) 20 mg or matching placebo for 7 days. Subjects were administered a single dose of 0.4 mg sublingual nitroglycerin (NTG) at pre-specified timepoints, following their last dose of Cialis(Tadalafil) (2, 4, 8, 24, 48, 72, and 96 hours after Cialis(Tadalafil)). The objective of the study was to determine when, after Cialis(Tadalafil) dosing, no apparent blood pressure interaction was observed. In this study, a significant interaction between Cialis(Tadalafil) and NTG was observed at each timepoint up to and including 24 hours. At 48 hours, by most hemodynamic measures, the interaction between Cialis(Tadalafil) and NTG was not observed, although a few more Cialis(Tadalafil) subjects compared to placebo experienced greater blood-pressure lowering at this timepoint. After 48 hours, the interaction was not detectable (see Figure 2). Figure 2: Mean Maximal Change in Blood Pressure (Cialis(Tadalafil) Minus Placebo, Point Estimate with 90% CI) in Response to Sublingual Nitroglycerin at 2 (Supine Only), 4, 8, 24, 48, 72, and 96 Hours after the Last Dose of Cialis(Tadalafil) 20 mg or Placebo Therefore, CIALIS administration with nitrates is contraindicated. In a patient who has taken CIALIS, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should elapse after the last dose of CIALIS before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring (see CONTRAINDICATIONS). Effects on Exercise Stress Testing — The effects of Cialis(Tadalafil) on cardiac function, hemodynamics, and exercise tolerance were investigated in a single clinical pharmacology study. In this blinded crossover trial, 23 subjects with stable coronary artery disease and evidence of exercise-induced cardiac ischemia were enrolled. The primary endpoint was time to cardiac ischemia. The mean difference in total exercise time was 3 seconds (Cialis(Tadalafil) 10 mg minus placebo), which represented no clinically meaningful difference. Further statistical analysis demonstrated that Cialis(Tadalafil) was non-inferior to placebo with respect to time to ischemia. Of note, in this study, in some subjects who received Cialis(Tadalafil) followed by sublingual nitroglycerin in the post-exercise period, clinically significant reductions in blood pressure were observed, consistent with the augmentation by Cialis(Tadalafil) of the blood-pressure-lowering effects of nitrates. Effects on Vision — Single oral doses of phosphodiesterase inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green), using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. In a study to assess the effects of a single dose of Cialis(Tadalafil) 40 mg on vision (N=59), no effects were observed on visual acuity, intraocular pressure, or pupillometry. Across all clinical studies with CIALIS, reports of changes in color vision were rare (<0.1% of patients). 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 Cialis(Tadalafil) 10 mg (N=204) or 20 mg (N=217) for 6 months. In addition, Cialis(Tadalafil) had no effect on serum levels of testosterone, luteinizing hormone, or follicle stimulating hormone. Effects on Cardiac Electrophysiology — The effect of a single 100-mg dose of Cialis(Tadalafil) on the QT interval was evaluated at the time of peak Cialis(Tadalafil) concentration in a randomized, double-blinded, placebo, and active (intravenous ibutilide)-controlled crossover study in 90 healthy males aged 18 to 53 years. The mean change in QTc (Fridericia QT correction) for Cialis(Tadalafil), relative to placebo, was 3.5 milliseconds (two-sided 90% CI=1.9, 5.1). The mean change in QTc (Individual QT correction) for Cialis(Tadalafil), relative to placebo, was 2.8 milliseconds (two-sided 90% CI=1.2, 4.4). A 100-mg dose of Cialis(Tadalafil) (5 times the highest recommended dose) was chosen because this dose yields exposures covering those observed upon coadministration of Cialis(Tadalafil) with potent CYP3A4 inhibitors or those observed in renal impairment. In this study, the mean increase in heart rate associated with a 100-mg dose of Cialis(Tadalafil) compared to placebo was 3.1 beats per minute. CLINICAL STUDIES The efficacy and safety of Cialis(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 daily, was shown to be effective in improving erectile function in men with erectile dysfunction (ED). Study Design — 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 daily. 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. 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. SEP Question 2 asks, "Were you able to insert your penis into your 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. Study Results — 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. In each of these 2 trials, CIALIS 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables (see Table 1). The treatment effect of CIALIS did not diminish over time. Table 1: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in the Two Primary US Trials Study A Study B Placebo CIALIS20 mg Placebo CIALIS20 mg (N=49) (N=146) p-value (N=48) (N=159) p-value EF Domain Score Endpoint 13.5 19.5 13.6 22.5 Change from baseline -0.2 6.9 <.001 0.3 9.3 <.001 Insertion of Penis (SEP2) Endpoint 39% 62% 43% 77% Change from baseline 2% 26% <.001 2% 32% <.001 Maintenance of Erection(SEP3) Endpoint 25% 50% 23% 64% Change from baseline 5% 34% <.001 4% 44% <.001 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 2, 3, and 4). The treatment effect of CIALIS did not diminish over time. Table 2: Mean Endpoint and Change from Baseline for the EF Domain of the IIEF in the General ED Population in Five Primary Trials Outside the US Placebo CIALIS5 mg CIALIS10 mg CIALIS20 mg Study C Endpoint [Change from baseline] 15.0 [0.7] 17.9 [4.0] 20.0 [5.6] p=.006 p<.001 Study D Endpoint [Change from baseline] 14.4 [1.1] 17.5 [5.1] 20.6 [6.0] p=.002 p<.001 Study E Endpoint [Change from baseline] 18.1 [2.6] 22.6 [8.1] 25.0 [8.0] p<.001 p<.001 Study F* Endpoint [Change from baseline] 12.7 [-1.6] 22.8 [6.8] p<.001 Study G Endpoint [Change from baseline] 14.5 [-0.9] 21.2 [6.6] 23.3 [8.0] p<.001 p<.001 * Treatment duration in Study F was 6 months Table 3: 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 US Placebo CIALIS5 mg CIALIS10 mg CIALIS20 mg Study C Endpoint [Change from baseline] 49% [6%] 57% [15%] 73% [29%] p=.063 p<.001 Study D Endpoint [Change from baseline] 46% [2%] 56% [18%] 68% [15%] p=.008 p<.001 Study E Endpoint [Change from baseline] 55% [10%] 77% [35%] 85% [35%] p<.001 p<.001 Study F* Endpoint [Change from baseline] 42% [-8%] 81% [27%] p<.001 Study G Endpoint [Change from baseline] 45% [-6%] 73% [21%] 76% [21%] p<.001 p<.001 * Treatment duration in Study F was 6 months Table 4: 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 US Placebo CIALIS5 mg CIALIS10 mg CIALIS20 mg Study C Endpoint [Change from baseline] 26% [4%] 38% [19%] 58% [32%] p=.040 p<.001 Study D Endpoint [Change from baseline] 28% [4%] 42% [24%] 51% [26%] p<.001 p<.001 Study E Endpoint [Change from baseline] 43% [15%] 70% [48%] 78% [50%] p<.001 p<.001 Study F* Endpoint [Change from baseline] 27% [1%] 74% [40%] p<.001 Study G Endpoint [Change from baseline] 32% [5%] 57% [33%] 62% [29%] p<.001 p<.001 * Treatment duration in Study F was 6 months In 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 CIALIS, compared to patients on placebo. Therefore, in all 7 primary efficacy and safety studies, CIALIS 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 in ED Patients with Diabetes Mellitus — CIALIS was 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 1 study that specifically assessed CIALIS in ED patients with type 1 or type 2 diabetes (N=216). In this randomized, placebo-controlled, double-blinded, parallel-arm design prospective trial, CIALIS 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 (see Table 5). Table 5: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Study in ED Patients with Diabetes Placebo CIALIS10 mg CIALIS20 mg (N=71) (N=73) (N=72) p-value EF Domain Score Endpoint [Change from baseline] 12.2 [0.1] 19.3 [6.4] 18.7 [7.3] <.001 Insertion of Penis (SEP2) Endpoint [Change from baseline] 30% [-4%] 57% [22%] 54% [23%] <.001 Maintenance of Erection (SEP3) Endpoint [Change from baseline] 20% [2%] 48% [28%] 42% [29%] <.001 Efficacy in ED Patients following Radical Prostatectomy — CIALIS was 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), CIALIS 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 (see Table 6). Table 6: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Study in Patients who Developed ED Following Bilateral Nerve-Sparing Radical Prostatectomy Placebo CIALIS20 mg (N=102) (N=201) p-value EF Domain Score Endpoint [Change from baseline] 13.3 [1.1] 17.7 [5.3] <.001 Insertion of Penis (SEP2) Endpoint [Change from baseline] 32% [2%] 54% [22%] <.001 Maintenance of Erection (SEP3) Endpoint [Change from baseline] 19% [4%] 41% [23%] <.001 Studies to Determine the Optimal Use of CIALIS — Several studies were conducted with the objective of determining the optimal use of CIALIS 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, CIALIS 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 CIALIS 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 CIALIS 20 mg. 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 CIALIS 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 CIALIS 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 CIALIS 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, CIALIS 10, or 20 mg) that were instructed to attempt intercourse at 2 different times (24 and 36 hours post-dosing). Patients were encouraged to make 4 separate attempts at their assigned dose and assigned timepoint. In this study, the results demonstrated a statistically significant difference between the placebo group and the CIALIS groups at each of the pre-specified timepoints. At the 24-hour timepoint, the mean, per-patient percentage of attempts resulting in successful intercourse were 42, 56, and 67% for the placebo, CIALIS 10-, and 20-mg groups, respectively. At the 36-hour timepoint, the mean, per-patient percentage of attempts resulting in successful intercourse were 33, 56, and 62% for placebo, CIALIS 10-, and 20-mg groups, respectively.

INDICATIONS AND USAGE (Cialis(Tadalafil)

INDICATIONS AND USAGE (Cialis(Tadalafil) CIALIS is indicated for the treatment of erectile dysfunction. DOSAGE AND ADMINISTRATIONThe recommended starting dose of CIALIS in most patients is 10 mg, taken prior to anticipated sexual activity. The dose may be increased to 20 mg or decreased to 5 mg, based on individual efficacy and tolerability. The maximum recommended dosing frequency is once per day in most patients. CIALIS was shown to improve erectile function compared to placebo up to 36 hours following dosing. Therefore, when advising patients on optimal use of CIALIS, this should be taken into consideration. CIALIS may be taken without regard to food. Renal Insufficiency — No dose adjustment is required in patients with mild renal insufficiency. For patients with moderate (creatinine clearance 31 to 50 mL/min) renal insufficiency, a starting dose of 5 mg not more than once daily is recommended, and the maximum dose should be limited to 10 mg not more than once in every 48 hours. For patients with severe (creatinine clearance <30 mL/min) renal insufficiency on hemodialysis, the maximum recommended dose is 5 mg (see General and Patients with Renal Insufficiency under PRECAUTIONS and Pharmacokinetics in Special Populations under CLINICAL PHARMACOLOGY). Hepatic Impairment — For patients with mild or moderate degrees of hepatic impairment (Child-Pugh Class A or B), the dose of CIALIS should not exceed 10 mg once daily. In patients with severe hepatic impairment (Child-Pugh Class C), the use of CIALIS is not recommended (see Patients with Hepatic Impairment under PRECAUTIONS and Pharmacokinetics in Special Populations under CLINICAL PHARMACOLOGY). Concomitant Medications When CIALIS is coadministered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating treatment with CIALIS, and CIALIS should be initiated at the lowest recommended dose (see PRECAUTIONS). For patients taking concomitant potent inhibitors of CYP3A4, such as ketoconazole or ritonavir, the maximum recommended dose of CIALIS is 10 mg, not to exceed once every 72 hours (see PRECAUTIONS). Concomitant use of nitrates in any form is contraindicated (see CONTRAINDICATIONS). Geriatrics — No dose adjustment is required in patients >65 years of age. HOW SUPPLIEDCIALISÒ (Cialis(Tadalafil)) is supplied as follows: Three strengths of film-coated, almond-shaped tablets are available in different sizes and different shades of yellow, and supplied in the following package sizes: 5-mg tablets debossed with "C 5" Bottles of 30 NDC 0002-4462-30 10-mg tablets debossed with "C 10" Bottles of 30 NDC 0002-4463-30 20-mg tablets debossed with "C 20" Bottles of 30 NDC 0002-4464-30 Store at 25° C (77° F); excursions permitted to 15-30° C (59-86° F) [see USP Controlled Room Temperature]. Keep out of reach of children.