Cialis Adverse Reactions
- back pain
- blepharedema
- blurred vision
- dyspepsia
- flushing
- headache
- myalgia
- nasal congestion
- priapism
- visual impairment
Adverse Reactions
Adverse reactions to tadalafil were evaluated based on worldwide clinical trials of tadalafil involving over 5700 men (mean age 59, range 19 to 87 years). Over 100 patients were treated for 1 year or longer and over 1300 were treated for 6 months or more. During placebo-controlled trials, the discontinuation rate for patients treated with tadalafil (10 or 20 mg) was 3.1% compared to 1.4% in placebo-treated patients. The adverse reactions occurring >= 2% of patients and more frequent in tadalafil-treated patients were headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and pain in limb. 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 was described as diffuse bilateral lower lumbar, gluteal, thigh, or thoracolumbar muscular discomfort and was exacerbated by recumbency. Generally, pain was reported as mild or moderate in severity and resolved without medical treatment; severe back pain was reported infrequently. When medical treatment was needed, acetaminophen or NSAIDs were generally effective; however, in a small number of patients who required treatment, a mild narcotic (e.g., codeine) was used. Overall, approximately 0.5% of all tadalafil-treated patients discontinued treatment due to back pain/myalgia. Diagnostic testing, including measures for inflammation, muscle injury, or renal damage revealed no medically significant underlying pathology. Blepharedema has also been reported rarely with tadalafil.
Adverse reactions that occurred less frequently (< 2%) with tadalafil and for which a causal relationship to tadalafil is uncertain include asthenia, facial edema, fatigue, pain, angina pectoris, chest pain, hypotension, hypertension, myocardial infarction, postural hypotension, palpitations, syncope, tachycardia, abnormal liver function tests, diarrhea, xerostomia, dysphagia, esophagitis, gastroesophageal reflux, gastritis, GGTP increased, loose stools, nausea/vomiting, upper abdominal pain, arthralgia, neck pain, dizziness, hypesthesia, insomnia, paresthesia, somnolence, vertigo, dyspnea, epistaxis, pharyngitis, pruritus, rash, diaphoresis, blurred vision, conjunctivitis (including conjunctival hyperemia), ocular pain, lacrimation increase, erection increased, spontaneous penile erection. Excluded from the list are those events that were minor, those with no plausible relation to tadalafil use, and reports too imprecise to be meaningful.
There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for PDE5 inhibitors. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention.
Tadalafil (20 mg) had no significant effect on supine or standing systolic and diastolic blood pressure in healthy male subjects compared to placebo. There was also no significant effect on heart rate.
The effects of 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 (tadalafil 10 mg minus placebo), which represented no clinically meaningful difference. Further statistical analysis demonstrated that tadalafil was non-inferior to placebo with respect to time to ischemia. Of note, in this study, in some subjects who received tadalafil followed by sublingual nitroglycerin in the post-exercise period, clinically significant reductions in blood pressure were observed, consistent with the augmentation by tadalafil of the blood-pressure-lowering effects of nitrates.
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 tadalafil 40 mg on vision (n=59), no effects were observed on visual acuity, intraocular pressure, or pupillometry. Across all clinical studies with tadalafil, reports of changes in color vision were rare (< 0.1% of patients). Post-marketing reports have included cases of visual impairment such as retinal vein occlusion and visual field defects. Nonarteritic ischemic optic neuropathy (NAION) has also been reported rarely in patients using phosphodiesterase type 5 (PDE5) inhibitors. It is thought that the vasoconstrictive effect of phosphodiesterase inhibitors may decrease blood flow to the optic nerve, especially in patients with a low cup to disk ratio. Symptoms, such as blurred vision and loss of visual field in one or both eyes, are usually reported within 24 hours of use. Most, but not all, of these patients who reported this adverse effect had underlying anatomic or vascular risk factors for development of NAION. These risk factors include, but are not limited to: low cup to disc ratio (’crowded disc’), age over 50 years, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. Additionally, two patients had retinal detachment and one patient had hypoplastic optic neuropathy. It is not yet possible to determine if these adverse 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.
There were no clinically relevant effects on sperm concentration, sperm count, motility, or morphology in humans in placebo-controlled studies of daily doses of tadalafil 10 mg (n=204) or 20 mg (n=217) for 6 months. In addition, tadalafil had no effect on serum levels of testosterone, luteinizing hormone, or follicle stimulating hormone.
The effect of a single 100-mg dose of tadalafil on the QT interval was evaluated at the time of peak 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 for tadalafil, relative to placebo, was 3.5 milliseconds. The mean change in QTc for tadalafil, relative to placebo, was 2.8 milliseconds. A 100-mg dose of tadalafil (5 times the highest recommended dose) was chosen because this dose yields exposures covering those observed upon coadministration of 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 tadalafil compared to placebo was 3.1 beats per minute.
[ Last revised: 7/11/2005 9:45:00 AM ]
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