FDA label c4b01de9-a780-476e-9d52-80c0d44f2ea9

5 WARNINGS AND PRECAUTIONS Evaluation of erectile dysfunction and BPH should include an appropriate medical assessment to identify potential underlying causes, as well as treatment options. Before prescribing CHEWTADZY, it is important to note the following: Cardiovascular Risk: Patients should not use CHEWTADZY if sex is inadvisable due to cardiovascular status (5.1). Hypotension When Used in Combination With Other Drugs and Alcohol: Use of CHEWTADZY with alpha blockers, anti- hypertensives, or substantial amounts of alcohol (≥ 5 units) may lead to hypotension. Not recommended for use in combination with alpha blockers for the treatment of BPH (5.6, 5.9, 7.1). Prolonged Erection and Priapism: Patients should seek emergency treatment if an erection lasts >4 hours. Use CHEWTADZY with caution in patients predisposed to priapism (5.3). Ocular Adverse Reactions: Patients should stop CHEWTADZY and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of non-arteritic anterior ischemic optic neuropathy (NAION). CHEWTADZY should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION. Patients with a "crowded" optic disc may also be at an increased risk of NAION (5.4, 6.2). Sudden Hearing Loss: Patients should stop CHEWTADZY and seek prompt medical attention in the event of sudden decrease or loss of hearing (5.5). Consideration of Other Urological Conditions Prior to Initiating Treatment for BPH: Prior to initiating treatment with CHEWTADZY for BPH, consider other urological conditions that may cause similar symptoms (5.14). 5.1 Cardiovascular Risk consider the cardiovascular status of patients, since there is a degree of cardiac risk associated with sexual activity. Therefore, treatments for erectile dysfunction, including CHEWTADZY, should not be used in men for whom sexual activity is inadvisable as a result of their underlying cardiovascular status. Patients who experience symptoms upon initiation of sexual activity should be advised to refrain from further sexual activity and seek immediate medical attention. discuss with patients the appropriate action in the event that they experience anginal chest pain requiring nitroglycerin following intake of CHEWTADZY. In such a patient, who has taken CHEWTADZY, where nitrate administration is deemed medically necessary for a life-threatening situation, at least 48 hours should have elapsed after the last dose of CHEWTADZY 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 CHEWTADZY should seek immediate medical attention [see Contraindications (4)] . Patients with left ventricular outflow obstruction, (e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators, including PDE5 inhibitors. The following groups of patients with cardiovascular disease were not included in clinical safety and efficacy trials for tadalafil, and therefore until further information is available, CHEWTADZY is not recommended for the following groups of patients: myocardial infarction within the last 90 days unstable angina or angina occurring during sexual intercourse New York Heart Association Class 2 or greater heart failure in the last 6 months uncontrolled arrhythmias, hypotension (<90/50 mm Hg), or uncontrolled hypertension stroke within the last 6 months. As with other PDE5 inhibitors, tadalafil has mild systemic vasodilatory properties that may result in transient decreases in blood pressure. In a clinical pharmacology study, tadalafil 20 mg resulted in a mean maximal decrease in supine blood pressure, relative to placebo, of 1.6/0.8 mm Hg in healthy subjects [see Clinical Pharmacology (12.2)] . While this effect should not be of consequence in most patients, prior to prescribing CHEWTADZY, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. Patients with severely impaired autonomic control of blood pressure may be particularly sensitive to the actions of vasodilators, including PDE5 inhibitors. 5.2 Potential for Drug Interactions When Taking CHEWTADZY for Once Daily Use CHEWTADZY for once daily use provides continuous plasma tadalafil levels. consider this when evaluating the potential for interactions with medications (e.g., nitrates, alpha- blockers, anti-hypertensives and potent inhibitors of CYP3A4) and with substantial consumption of alcohol [see Drug Interactions (7)] . 5.3 Prolonged Erection and Priapism Instruct patients who have an erection lasting greater than 4 hours, whether painful or not, to seek emergency medical attention. Use CHEWTADZY with caution in patients who have conditions that might predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. 5.4 Ocular Adverse Reactions Advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including CHEWTADZY, and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5-11.8 cases per 100,000 in males aged 50 years and older. An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of "crowded" optic disc, may have contributed to the occurrence of NAION in these studies. Neither the rare postmarketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [see Adverse Reactions (6.2)] . Consider whether patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, use PDE5 inhibitors, including CHEWTADZY, with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with "crowded" optic disc are also considered at greater risk for NAION compared to the general population; however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including CHEWTADZY, for this uncommon condition. Patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, were not included in the clinical trials, and use of CHEWTADZY in these patients is not recommended. 5.5 Sudden Hearing Loss Advise patients to stop taking CHEWTADZY and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including tadalafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, such as CHEWTADZY, or to other factors [see Adverse Reactions (6.1, 6.2)] . 5.6 Hypotension with Concomitant Use of Alpha-blockers and Antihypertensives Discuss with patients the potential for CHEWTADZY to augment the blood-pressure-lowering effect of alpha-blockers and antihypertensive medications [see Drug Interactions (7.1) and Clinical Pharmacology (12.2)] . Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including CHEWTADZY, and alpha-adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. In some patients, concomitant use of these two drug classes can lower blood pressure significantly [see Drug Interactions (7.1) and Clinical Pharmacology (12.2)] , which may lead to symptomatic hypotension (e.g., fainting). Consideration should be given to the following: ED Prior to initiating CHEWTADZY, a PDE5 inhibitor, ensure that patients are stable on alpha-blocker therapy. Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors. Initiate CHEWTADZY at the lowest recommended dose in patients who are stable on alpha-blocker therapy. In those patients already taking an optimized dose of PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure when taking a PDE5 inhibitor. Safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other variables, including intravascular volume depletion and other antihypertensive drugs [see Dosage and Administration (2.7) and Drug Interactions (7.1)] . BPH The efficacy of the coadministration of an alpha-blocker and tadalafil for the treatment of BPH has not been adequately studied, and due to the potential vasodilatory effects of combined use resulting in blood pressure lowering, the combination of CHEWTADZY and alpha-blockers is not recommended for the treatment of BPH [see Dosage and Administration (2.7), Drug Interactions (7.1), and Clinical Pharmacology (12.2.)] . Discontinue alpha-blockers at least one day prior to starting CHEWTADZY for once daily use for the treatment of BPH. 5.7 Hypotension with Concomitant Use of Alcohol Inform patients that both alcohol and CHEWTADZY, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Inform patients that substantial consumption of alcohol (e.g., 5 units or greater) in combination with CHEWTADZY can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache [see Clinical Pharmacology (12.2)] . 5.8 Concomitant Use with Potent Inhibitors of Cytochrome P450 3A4 (CYP3A4) CHEWTADZY is metabolized predominantly by CYP3A4 in the liver. The dose of CHEWTADZY for use as needed should be limited to 10 mg no more than once every 72 hours in patients taking potent inhibitors of CYP3A4 such as ritonavir, ketoconazole, and itraconazole [see Drug Interactions (7.2)] . CHEWTADZY is not recommended in patients taking potent inhibitors of CYP3A4 due to the lack of a 2.5 mg strength [see Dosage and Administration (2.7)] . 5.9 Combination with Other PDE5 Inhibitors or Erectile Dysfunction Therapies The safety and efficacy of combinations of tadalafil and other PDE5 inhibitors or treatments for erectile dysfunction have not been studied. Inform patients not to take CHEWTADZY with other PDE5 inhibitors, including ADCIRCA. 5.10 Effects on Bleeding Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in platelets. When administered in combination with aspirin, tadalafil 20 mg did not prolong bleeding time, relative to aspirin alone. Tadalafil has not been administered to patients with bleeding disorders or significant active peptic ulceration. Although tadalafil has not been shown to increase bleeding times in healthy subjects, use in patients with bleeding disorders or significant active peptic ulceration should be based upon a careful risk-benefit assessment and caution. 5.11 Counseling Patients about Sexually Transmitted Diseases The use of CHEWTADZY offers no protection against sexually transmitted diseases. Counseling patients about the protective measures necessary to guard against sexually transmitted diseases, including Human Immunodeficiency Virus (HIV) should be considered. 5.12 Consideration of Other Urological Conditions Prior to Initiating Treatment for BPH Prior to initiating treatment with CHEWTADZY for BPH, consider whether patients have other urological conditions that may cause similar symptoms. In addition, prostate cancer and BPH may coexist.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Cardiovascular Risk [ see Warnings and Precautions (5.1)] Prolonged Erection and Priapism [see Warnings and Precautions (5.3)] Ocular Adverse Reactions [see Warnings and Precautions (5.4)] Sudden Hearing Loss [see Warnings and Precautions (5.5)] Effects on Bleeding [ see Warnings and Precautions (5.12)] Most common adverse reactions (≥2%) include headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and pain in limb (6.1). To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience 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 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 tadalafil for use as needed, over 1300 and 1000 subjects were treated for at least 6 months and 1 year, respectively. CHEWTADZY for Use as Needed for ED In eight primary placebo-controlled clinical studies of 12 weeks duration, mean age was 59 years (range 22 to 88) and the discontinuation rate due to adverse reactions in patients treated with tadalafil 10 or 20 mg was 3.1%, compared to 1.4% in placebo treated patients. When taken as recommended in the placebo-controlled clinical trials, the following adverse reactions were reported ( see Table 4) for tadalafil for use as needed: Table 4: Treatment-Emergent Adverse Reactions Reported by ≥2% of Patients Treated with Tadalafil (10 or 20 mg) and More Frequent on Drug than Placebo in the Eight Primary Placebo-Controlled Clinical Studies (Including a Study in Patients with Diabetes) for Tadalafil for Use as Needed for ED Adverse Reaction Placebo (N=476) Tadalafil 5 mg (N=151) Tadalafil 10 mg (N=394) Tadalafil 20 mg (N=635) Headache 5% 11% 11% 15% Dyspepsia 1% 4% 8% 10% Back pain 3% 3% 5% 6% Myalgia 1% 1% 4% 3% Nasal congestion 1% 2% 3% 3% Flushing a 1% 2% 3% 3% Pain in limb 1% 1% 3% 3% a The term flushing includes: facial flushing and flushing CHEWTADZY for Once Daily Use for BPH and for ED and BPH In three placebo-controlled clinical trials of 12 weeks duration, two in patients with BPH and one in patients with ED and BPH, the mean age was 63 years (range 44 to 93) and the discontinuation rate due to adverse reactions in patients treated with tadalafil was 3.6% compared to 1.6% in placebo-treated patients. Adverse reactions leading to discontinuation reported by at least 2 patients treated with tadalafil included headache, upper abdominal pain, and myalgia. The following adverse reactions were reported ( see Table 5). Table 5: Treatment-Emergent Adverse Reactions Reported by ≥1% of Patients Treated with Tadalafil for Once Daily Use (5 mg) and More Frequent on Drug than Placebo in Three Placebo-Controlled Clinical Studies of 12 Weeks Treatment Duration, including Two Studies for Tadalafil for Once Daily Use for BPH and One Study for ED and BPH Adverse Reaction Placebo (N=576) Tadalafil 5 mg (N=581) Headache 2.3% 4.1% Dyspepsia 0.2% 2.4% Back pain 1.4% 2.4% Nasopharyngitis 1.6% 2.1% Diarrhea 1.0% 1.4% Pain in extremity 0.0% 1.4% Myalgia 0.3% 1.2% Dizziness 0.5% 1.0% Additional, less frequent adverse reactions (<1%) reported in the controlled clinical trials of tadalafil for BPH or ED and BPH included: gastroesophageal reflux disease, upper abdominal pain, nausea, vomiting, arthralgia, and muscle spasm. Back pain or myalgia was reported at incidence rates described in Tables 4 and 5. 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 and was exacerbated by recumbency. In general, pain was reported as mild or moderate in severity and resolved without medical treatment, but severe back pain was reported with a low frequency (<5% of all reports). When medical treatment was necessary, acetaminophen or non-steroidal anti-inflammatory drugs were generally effective; however, in a small percentage of subjects who required treatment, a mild narcotic (e.g., codeine) was used. Overall, approximately 0.5% of all subjects treated with tadalafil for on demand use discontinued treatment as a consequence of back pain/myalgia. In the 1-year open label extension study, back pain and myalgia were reported in 5.5% and 1.3% of patients, respectively. Diagnostic testing, including measures for inflammation, muscle injury, or renal damage revealed no evidence of medically significant underlying pathology. Incidence rates for tadalafil for once daily use for ED, BPH and BPH/ED are described in Table 2. In studies of tadalafil for once daily use, adverse reactions of back pain and myalgia were generally mild or moderate with a discontinuation rate of <1% across all indications. Across placebo-controlled studies with tadalafil for use as needed for ED, diarrhea was reported more frequently in patients 65 years of age and older who were treated with tadalafil (2.5% of patients) [see Use in Specific Populations (8.5)] . Across all studies with any tadalafil dose, reports of changes in color vision were rare (<0.1% of patients). The following section identifies additional, less frequent events (<2%) reported in controlled clinical trials of tadalafil for once daily use or use as needed. A causal relationship of these events to tadalafil is uncertain. Excluded from this list are those events that were minor, those with no plausible relation to drug use, and reports too imprecise to be meaningful: Body as a Whole — asthenia, face edema, fatigue, pain, peripheral edema Cardiovascular — angina pectoris, chest pain, hypotension, myocardial infarction, postural hypotension, palpitations, syncope, tachycardia Digestive — abnormal liver function tests, dry mouth, dysphagia, esophagitis, gastritis, GGTP increased, loose stools, nausea, upper abdominal pain, vomiting, gastroesophageal reflux disease, hemorrhoidal hemorrhage, rectal hemorrhage Musculoskeletal — arthralgia, neck pain Nervous — dizziness, hypesthesia, insomnia, paresthesia, somnolence, vertigo Renal and Urinary — renal impairment Respiratory — dyspnea, epistaxis, pharyngitis Skin and Appendages — pruritus, rash, sweating Ophthalmologic — blurred vision, changes in color vision, conjunctivitis (including conjunctival hyperemia), eye pain, lacrimation increase, swelling of eyelids Otologic — sudden decrease or loss of hearing, tinnitus Urogenital — erection increased, spontaneous penile erection 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of 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. Cardiovascular and Cerebrovascular — Serious cardiovascular events, including myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations, and tachycardia, have been reported postmarketing in temporal association with the use of tadalafil. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of tadalafil without sexual activity. Others were reported to have occurred hours to days after the use of tadalafil and sexual activity. It is not possible to determine whether these events are related directly to tadalafil, to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors [see Warnings and Precautions (5.1)] . Body as a Whole — hypersensitivity reactions including urticaria, Stevens-Johnson syndrome, and exfoliative dermatitis Nervous — migraine, seizure and seizure recurrence, transient global amnesia Ophthalmologic — visual field defect, retinal vein occlusion, retinal artery occlusion 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 PDE5 inhibitors, including 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 [see Warnings and Precautions (5.4)] . Otologic — Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including tadalafil. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of tadalafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Warnings and Precautions (5.5)] . Urogenital — priapism [see Warnings and Precautions (5.3)] .

<table cellspacing="0" cellpadding="0" border="0" width="646"><colgroup><col width="21.9572623103128%"/><col width="19.5106844224218%"/><col width="20.4397646330133%"/><col width="18.5816042118303%"/><col width="19.5106844224218%"/></colgroup><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="middle"><content styleCode="bold">Adverse Reaction</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Placebo</content> <content styleCode="bold">(N=476)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Tadalafil 5 mg</content> <content styleCode="bold">(N=151)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Tadalafil 10 mg</content> <content styleCode="bold">(N=394)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Tadalafil 20 mg</content> <content styleCode="bold">(N=635)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Headache</content> </td><td styleCode="Rrule" align="center" valign="middle">5% </td><td styleCode="Rrule" align="center" valign="middle">11% </td><td styleCode="Rrule" align="center" valign="middle">11% </td><td styleCode="Rrule" align="center" valign="middle">15% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Dyspepsia</content> </td><td styleCode="Rrule" align="center" valign="middle">1% </td><td styleCode="Rrule" align="center" valign="middle">4% </td><td styleCode="Rrule" align="center" valign="middle">8% </td><td styleCode="Rrule" align="center" valign="middle">10% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Back pain</content> </td><td styleCode="Rrule" align="center" valign="middle">3% </td><td styleCode="Rrule" align="center" valign="middle">3% </td><td styleCode="Rrule" align="center" valign="middle">5% </td><td styleCode="Rrule" align="center" valign="middle">6% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Myalgia</content> </td><td styleCode="Rrule" align="center" valign="middle">1% </td><td styleCode="Rrule" align="center" valign="middle">1% </td><td styleCode="Rrule" align="center" valign="middle">4% </td><td styleCode="Rrule" align="center" valign="middle">3% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Nasal congestion</content> </td><td styleCode="Rrule" align="center" valign="middle">1% </td><td styleCode="Rrule" align="center" valign="middle">2% </td><td styleCode="Rrule" align="center" valign="middle">3% </td><td styleCode="Rrule" align="center" valign="middle">3% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Flushing^a</content> </td><td styleCode="Rrule" align="center" valign="middle">1% </td><td styleCode="Rrule" align="center" valign="middle">2% </td><td styleCode="Rrule" align="center" valign="middle">3% </td><td styleCode="Rrule" align="center" valign="middle">3% </td></tr><tr><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Pain in limb</content> </td><td styleCode="Rrule" align="center" valign="middle">1% </td><td styleCode="Rrule" align="center" valign="middle">1% </td><td styleCode="Rrule" align="center" valign="middle">3% </td><td styleCode="Rrule" align="center" valign="middle">3% </td></tr></tbody></table>

<table cellspacing="0" cellpadding="0" border="0" width="490"><colgroup><col width="30.1755818701511%"/><col width="29.3997550020417%"/><col width="40.4246631278073%"/></colgroup><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="middle"><content styleCode="bold">Adverse Reaction</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Placebo</content> <content styleCode="bold">(N=576)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Tadalafil 5 mg</content> <content styleCode="bold">(N=581)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Headache</content> </td><td styleCode="Rrule" align="center" valign="middle">2.3% </td><td styleCode="Rrule" align="center" valign="middle">4.1% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Dyspepsia</content> </td><td styleCode="Rrule" align="center" valign="middle">0.2% </td><td styleCode="Rrule" align="center" valign="middle">2.4% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Back pain</content> </td><td styleCode="Rrule" align="center" valign="middle">1.4% </td><td styleCode="Rrule" align="center" valign="middle">2.4% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Nasopharyngitis</content> </td><td styleCode="Rrule" align="center" valign="middle">1.6% </td><td styleCode="Rrule" align="center" valign="middle">2.1% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Diarrhea</content> </td><td styleCode="Rrule" align="center" valign="middle">1.0% </td><td styleCode="Rrule" align="center" valign="middle">1.4% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Pain in extremity</content> </td><td styleCode="Rrule" align="center" valign="middle">0.0% </td><td styleCode="Rrule" align="center" valign="middle">1.4% </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Myalgia</content> </td><td styleCode="Rrule" align="center" valign="middle">0.3% </td><td styleCode="Rrule" align="center" valign="middle">1.2% </td></tr><tr><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Dizziness</content> </td><td styleCode="Rrule" align="center" valign="middle">0.5% </td><td styleCode="Rrule" align="center" valign="middle">1.0% </td></tr></tbody></table>