Vardenafilside effects

The following serious adverse reactions with the use of vardenafil orally disintegrating tablet are discussed elsewhere in the labeling: Cardiovascular effects Priapism QT Prolongation Effects on eye Sudden hearing loss Adverse reactions reported by ≥ 2% of patients treated with vardenafil orally disintegrating tablet: Headache, flushing, nasal congestion, dyspepsia, dizziness, back pain. To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc., at 1-888-943-3210 or 1-855-926-3384 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical

Studies 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.

Vardenafil orally disintegrating tablet: Safety of vardenafil orally disintegrating tablet was evaluated in two identical multi-national, randomized, double-blind, placebo-controlled trials. In both pivotal studies, enrollment was stratified so that approximately 50% of patients were ≥65 years old. Approximately 8% (n=29) were ≥75 years old. An integrated analysis of both studies included a total of 355 subjects that received vardenafil orally disintegrating tablet compared to 340 subjects that received placebo (mean age was 61.7, range 21.0 to 88.0; 68% White, 5% Black, 6% Asian, 11% Hispanic and 11% Other). The discontinuation rates due to adverse reactions were 1.4% for vardenafil orally disintegrating tablet compared to 0.6% for placebo. Table 1 below details the most frequently reported adverse reactions.

Table 1: Adverse drug reactions reported by ≥2% of the patients treated with vardenafil orally disintegrating tablet and more frequent on drug than placebo in controlled trials Adverse Drug Reaction Vardenafil Orally Disintegrating Tablet (n=355) Placebo (n=340) Headache 14.4% 1.8% Flushing 7.6% 0.6% Nasal Congestion 3.1% 0.3% Dyspepsia 2.8% 0% Dizziness 2.3% 0% Back Pain 2% 0.3% Adverse drug reactions reported in the vardenafil orally disintegrating tablet placebo controlled trials were comparable to the adverse drug reactions reported in earlier vardenafil film-coated tablets placebo controlled trials.

All Vardenafil Studies: Vardenafil film-coated tablets and vardenafil orally disintegrating tablet has been administered to over 17,000 men (mean age 54.5, range 18–89 years; 70% White, 5% Black, 13% Asian, 4% Hispanic and 8% Other) during controlled and uncontrolled clinical trials worldwide. The number of patients treated for 6 months or longer was 3357, and 1350 patients were treated for at least 1 year. In the placebo-controlled clinical trials for vardenafil film-coated tablets and vardenafil orally disintegrating tablet, the discontinuation rate due to adverse events was 1.9% for vardenafil compared to 0.8% for placebo. Placebo-controlled trials suggested a dose effect in the incidence of some adverse reactions (for example, dizziness, headache, flushing, dyspepsia, nausea, nasal congestion) over the 5 mg, 10 mg, and 20 mg doses of vardenafil film-coated tablets. The following section identifies additional, less frequent adverse reactions (<2%) reported during the clinical development of vardenafil film-coated tablets and vardenafil orally disintegrating tablet. Excluded from this list are those adverse reactions that are infrequent and minor, those events that may be commonly observed in the absence of drug therapy, and those events that are not reasonably associated with the drug: Body as a whole: allergic edema and angioedema, feeling unwell, allergic reactions, chest pain Auditory: tinnitus, vertigo Cardiovascular: palpitation, tachycardia, angina pectoris, myocardial infarction, ventricular tachyarrhythmias, hypotension Digestive: nausea, gastrointestinal and abdominal pain, dry mouth, diarrhea, gastroesophageal reflux disease, gastritis, vomiting, increase in transaminases Musculoskeletal: increase in creatine phosphokinase (CPK), increased muscle tone and cramping, myalgia Nervous: paresthesia and dysesthesia, somnolence, sleep disorder, syncope, amnesia, seizure Respiratory: dyspnea, sinus congestion Skin and appendages: erythema, rash Ophthalmologic: visual disturbance, ocular hyperemia, visual color distortions, eye pain and eye discomfort, photophobia, increase in intraocular pressure, conjunctivitis Urogenital: increase in erection, priapism

6.2 Postmarketing

Experience The following adverse reactions have been identified during post approval use of vardenafil in the film-coated tablet formulation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

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 PDE5 inhibitors, including vardenafil. 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. Visual disturbances including vision loss (temporary or permanent), such as visual field defect, retinal vein occlusion, and reduced visual acuity, have also been reported rarely in postmarketing experience. It is not possible to determine whether these events are related directly to the use of vardenafil.

Neurologic: Seizure, seizure recurrence and transient global amnesia have been reported postmarketing in temporal association with vardenafil.

Otologic: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. In some 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 vardenafil, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors.