Cialis Information
Cialis (Tadalafil) Dosage And Administration
Cialis (Tadalafil) Dosage Forms And Strengths
Four strengths of almond-shaped tablets are available in different sizes and different shades of yellow:
Cialis (Tadalafil) Contraindications
[see Adverse Reactions ()]
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Cialis (Tadalafil) Warnings And Precautions
Before prescribing Cialis (Tadalafil) , it is important to note the following:
Cialis (Tadalafil) Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Tadalafil was administered to over 9000 men during clinical trials worldwide. In trials of Cialis (Tadalafil) for once daily use, a total of 1434, 905, and 115 were treated for at least 6 months, 1 year, and 2 years, respectively. For Cialis (Tadalafil) for use as needed, over 1300 and 1000 subjects were treated for at least 6 months and 1 year, respectively.
The following adverse reactions have been identified during post approval use of Cialis (Tadalafil) . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion either due to their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors.
Body as a Whole
Nervous
Ophthalmologic
Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including Cialis (Tadalafil) . Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors .
Cialis (Tadalafil) Drug Interactions
[See Dosage and Administration () and Warnings and Precautions ()]
Cialis (Tadalafil) Use In Specific Populations
Cialis (Tadalafil) is not indicated for use in women. It is not known whether tadalafil is excreted into human milk. While tadalafil or some metabolite of tadalafil was excreted into rat milk, drug levels in animal breast milk may not accurately predict levels of drug in human breast milk.
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.
Cialis (Tadalafil) Overdosage
Single doses up to 500 mg have been given to healthy subjects, and multiple daily doses up to 100 mg have been given to patients. Adverse events were similar to those seen at lower doses. In cases of overdose, standard supportive measures should be adopted as required. Hemodialysis contributes negligibly to tadalafil elimination.
Cialis (Tadalafil) Description
Cialis (Tadalafil) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Tadalafil has the empirical formula CHNO representing a molecular weight of 389.41. The structural formula is:
The chemical designation is pyrazino[1´,2´: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 (Tadalafil) is available as almond-shaped tablets for oral administration. Each tablet contains 2.5, 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.
Cialis (Tadalafil) Clinical Pharmacology
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. Tadalafil inhibits PDE5. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by tadalafil has no effect in the absence of sexual stimulation.
The effect of PDE5 inhibition on cGMP concentration in the corpus cavernosum and pulmonary arteries is also observed in the smooth muscle of the prostate, the bladder and their vascular supply. The mechanism for reducing BPH symptoms has not been established.
Studies have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in the smooth muscle of the corpus cavernosum, prostate, and bladder as well as in vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas.
Cialis (Tadalafil) Clinical Studies
The 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 (Tadalafil) , 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 (Tadalafil) 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 (Tadalafil) 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. Food and alcohol intake were not restricted.
Several assessment tools were used to evaluate the effect of Cialis (Tadalafil) 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 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.
The efficacy and safety of Cialis (Tadalafil) for once daily use in the treatment of erectile dysfunction has been evaluated in 2 clinical trials of 12-weeks duration and 1 clinical trial of 24-weeks duration, involving a total of 853 patients. Cialis (Tadalafil) , when taken once daily, was shown to be effective in improving erectile function in men with erectile dysfunction (ED).
Cialis (Tadalafil) was studied in the general ED population in 2 randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design, primary efficacy and safety studies of 12- and 24-weeks duration, respectively. One of these studies was conducted in the United States and one was conducted in centers outside the US. An additional efficacy and safety study was performed in ED patients with diabetes mellitus. Cialis (Tadalafil) was taken once daily at doses ranging from 2.5 to 10 mg. Food and alcohol intake were not restricted. Timing of sexual activity was not restricted relative to when patients took Cialis (Tadalafil) .
The efficacy and safety of Cialis (Tadalafil) for once daily use for the treatment of the signs and symptoms of BPH was evaluated in 3 randomized, multinational, double-blinded, placebo-controlled, parallel-design, efficacy and safety studies of 12 weeks duration. Two of these studies were in men with BPH and one study was specific to men with both ED and BPH . The first study (Study J) randomized 1058 patients to receive either Cialis (Tadalafil) 2.5 mg, 5 mg, 10 mg or 20 mg for once daily use or placebo. The second study (Study K) randomized 325 patients to receive either Cialis (Tadalafil) 5 mg for once daily use or placebo. The full study population was 87% White, 2% Black, 11% other races; 15% was of Hispanic ethnicity. Patients with multiple co-morbid conditions such as diabetes mellitus, hypertension, and other cardiovascular disease were included.
The primary efficacy endpoint in the two studies that evaluated the effect of Cialis (Tadalafil) for the signs and symptoms of BPH was the International Prostate Symptom Score (IPSS), a four week recall questionnaire that was administered at the beginning and end of a placebo run-in period and subsequently at follow-up visits after randomization. The IPSS assesses the severity of irritative (frequency, urgency, nocturia) and obstructive symptoms (incomplete emptying, stopping and starting, weak stream, and pushing or straining), with scores ranging from 0 to 35; higher numeric scores representing greater severity. Maximum urinary flow rate (Q), an objective measure of urine flow, was assessed as a secondary efficacy endpoint in Study J and as a safety endpoint in Study K.
The results for BPH patients with moderate to severe symptoms and a mean age of 63.2 years (range 44 to 87) who received either Cialis (Tadalafil) 5 mg for once daily use or placebo (N=748) in Studies J and K are shown in and and , respectively.
In each of these 2 trials, Cialis (Tadalafil) 5 mg for once daily use resulted in statistically significant improvement in the total IPSS compared to placebo. Mean total IPSS showed a decrease starting at the first scheduled observation (4 weeks) in Study K and remained decreased through 12 weeks.
In Study J, the effect of Cialis (Tadalafil) 5 mg once daily on maximum urinary flow rate (Q) was evaluated as a secondary efficacy endpoint. Mean Q increased from baseline in both the treatment and placebo groups (Cialis (Tadalafil) 5 mg: 1.6 mL/sec, placebo: 1.2 mL/sec); however, these changes were not significantly different between groups.
In Study K, the effect of Cialis (Tadalafil) 5 mg once daily on Q was evaluated as a safety endpoint. Mean Q increased from baseline in both the treatment and placebo groups (Cialis (Tadalafil) 5 mg: 1.6 mL/sec, placebo: 1.1 mL/sec); however, these changes were not significantly different between groups.
The efficacy and safety of Cialis (Tadalafil) for once daily use for the treatment of ED, and the signs and symptoms of BPH, in patients with both conditions was evaluated in one placebo-controlled, multinational, double-blind, parallel-arm study which randomized 606 patients to receive either Cialis (Tadalafil) 2.5 mg, 5 mg, for once daily use or placebo. ED severity ranged from mild to severe and BPH severity ranged from moderate to severe. The full study population had a mean age of 63 years (range 45 to 83) and was 93% White, 4% Black, 3% other races; 16% were of Hispanic ethnicity. Patients with multiple co-morbid conditions such as diabetes mellitus, hypertension, and other cardiovascular disease were included.
In this study, the co-primary endpoints were total IPSS and the Erectile Function (EF) domain score of the International Index of Erectile Function (IIEF). One of the key secondary endpoints in this study was Question 3 of the Sexual Encounter Profile diary (SEP3). Timing of sexual activity was not restricted relative to when patients took Cialis (Tadalafil) .
The efficacy results for patients with both ED and BPH, who received either Cialis (Tadalafil) 5 mg for once daily use or placebo (N=408) are shown in and and .
Cialis (Tadalafil) 5 mg for once daily use resulted in statistically significant improvements in the total IPSS and in the EF domain of the IIEF questionnaire. Cialis (Tadalafil) 5 mg for once daily use also resulted in statistically significant improvement in SEP3. Cialis (Tadalafil) 2.5 mg did not result in statistically significant improvement in the total IPSS.
Cialis (Tadalafil) for once daily use resulted in improvement in the IPSS total score at the first scheduled observation (week 2) and throughout the 12 weeks of treatment (
).
In this study, the effect of Cialis (Tadalafil) 5 mg once daily on Q was evaluated as a safety endpoint. Mean Q increased from baseline in both the treatment and placebo groups (Cialis (Tadalafil) 5 mg: 1.6 mL/sec, placebo: 1.2 mL/sec); however, these changes were not significantly different between groups.
Cialis (Tadalafil) How Supplied/storage And Handling
Cialis (Tadalafil) is supplied as follows:
Four strengths of almond-shaped tablets are available in different sizes and different shades of yellow, and supplied in the following package sizes:
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.
Cialis (Tadalafil) Patient Counseling Information
“See FDA-approved Patient Labeling ()”
Physicians should discuss with patients the contraindication of Cialis (Tadalafil) with regular and/or intermittent use of organic nitrates. Patients should be counseled that concomitant use of Cialis (Tadalafil) with nitrates could cause blood pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke.
Physicians should discuss with patients the appropriate action in the event that they experience anginal chest pain requiring nitroglycerin following intake of Cialis (Tadalafil) . In such a patient, who has taken Cialis (Tadalafil) , where nitrate administration is deemed medically necessary for a life-threatening situation, at least 48 hours should have elapsed after the last dose of Cialis (Tadalafil) before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring. Therefore, patients who experience anginal chest pain after taking Cialis (Tadalafil) should seek immediate medical attention .
Physicians should instruct patients on the appropriate administration of Cialis (Tadalafil) to allow optimal use.
For Cialis (Tadalafil) for use as needed in men with ED, patients should be instructed to take one tablet at least 30 minutes before anticipated sexual activity. In most patients, the ability to have sexual intercourse is improved for up to 36 hours.
For Cialis (Tadalafil) for once daily use in men with ED or ED/BPH, patients should be instructed to take one tablet at approximately the same time every day without regard for the timing of sexual activity. Cialis (Tadalafil) is effective at improving erectile function over the course of therapy.
For Cialis (Tadalafil) for once daily use in men with BPH, patients should be instructed to take one tablet at approximately the same time every day.
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