Generic: VARDENAFIL
1 INDICATIONS & USAGE Vardenafil orally disintegrating tablet is indicated for the treatment of erectile dysfunction. Vardenafil is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction. ( 1 )
5 WARNINGS AND PRECAUTIONS The evaluation of erectile dysfunction should include a medical assessment, a determination of potential underlying causes and the identification of appropriate treatment. Before prescribing vardenafil orally disintegrating tablet, it is important to note the following: Cardiovascular Effects: Patients should not use vardenafil orally disintegrating tablet if sex is inadvisable due to cardiovascular status. ( 5.1 ) Strong and Moderate CYP3A4 Inhibitors: Do not use vard...
5 WARNINGS AND PRECAUTIONS The evaluation of erectile dysfunction should include a medical assessment, a determination of potential underlying causes and the identification of appropriate treatment. Before prescribing vardenafil orally disintegrating tablet, it is important to note the following: Cardiovascular Effects: Patients should not use vardenafil orally disintegrating tablet if sex is inadvisable due to cardiovascular status. ( 5.1 ) Strong and Moderate CYP3A4 Inhibitors: Do not use vardenafil orally disintegrating tablet in patients taking strong or moderate CYP3A4 inhibitors. ( 5.2 , 7.2 ) Risk of Priapism: In the event that an erection lasts more than 4 hours, the patient should seek immediate medical assistance. ( 5.3 ) Effects on the Eye: Patients should stop use of vardenafil orally disintegrating tablet, and seek medical attention in the event of sudden loss of vision in one or both eyes, which could be a sign of non arteritic anterior ischemic optic neuropathy (NAION). Vardenafil orally disintegrating tablet 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 vardenafil orally disintegrating tablet and seek medical attention in the event of sudden decrease or loss in hearing. ( 5.5 , 6.2 ) Alpha-Blockers: Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. In some patients, concomitant use of these two drug classes can lower blood pressure significantly leading to symptomatic hypotension (for example, fainting). In patients taking alpha-blockers, do not initiate vardenafil therapy with vardenafil orally disintegrating tablet. ( 2.4, 5.6 ) QT Prolongation: Patients with congenital QT syndrome or taking class IA or III antiarrhythmics should avoid using vardenafil orally disintegrating tablet. ( 5.7 , 12.2 ) Phenylketonurics: Each vardenafil orally disintegrating tablet contains 3.36 mg phenylalanine per tablet, which could be harmful for patients with phenylketonuria. ( 5.12) 5.1 Cardiovascular Effects General Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Therefore, treatment for erectile dysfunction, including vardenafil orally disintegrating tablet, should not be used in men for whom sexual activity is not recommended because of their underlying cardiovascular status. There are no controlled clinical data on the safety or efficacy of vardenafil in the following patients; and therefore its use is not recommended until further information is available: unstable angina; hypotension (resting systolic blood pressure of <90 mmHg); uncontrolled hypertension (>170/110 mmHg); recent history of stroke, life-threatening arrhythmia, or myocardial infarction (within the last 6 months); severe cardiac failure. Left Ventricular Outflow Obstruction Patients with left ventricular outflow obstruction (for example, aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators including PDE5 inhibitors. Blood Pressure Effects Vardenafil has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 7 mmHg systolic and 8 mmHg diastolic) [see Clinical Pharmacology ( 12.2 )] . While this normally would be expected to be of little consequence in most patients, prior to prescribing vardenafil orally disintegrating tablet, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. 5.2 Potential for Drug Interactions with Strong or Moderate CYP3A4 Inhibitors Concomitant administration with strong CYP3A4 inhibitors (such as ritonavir, indinavir, ketoconazole and cobicistat) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. Do not use vardenafil orally disintegrating tablet in patients taking strong or moderate CYP3A4 inhibitors. [See Dosage and Administration ( 2.4 ), Drug Interactions ( 7.2 ) and Patient Counseling Information ( 17 ).] 5.3 Risk of Priapism 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, including vardenafil. In the event that an erection persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result. Vardenafil orally disintegrating tablet should be used with caution by patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease) or by patients who have conditions that may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia). 5.4 Effects on the Eye Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including vardenafil orally disintegrating tablet, and seek medical attention in the event of 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. 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 )] . Physicians should consider whether their 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, PDE5 inhibitors, including vardenafil orally disintegrating tablet, should be used 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 vardenafil orally disintegrating tablet, for this uncommon condition. Vardenafil orally disintegrating tablet has not been evaluated in patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, therefore its use is not recommended until further information is available in those patients. 5.5 Sudden Hearing Loss Physicians should advise patients to stop taking all PDE5 inhibitors, including vardenafil orally disintegrating tablet, 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 vardenafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions ( 6.2 )]. 5.6 Alpha-Blockers In patients taking alpha-blockers, do not initiate vardenafil therapy with vardenafil orally disintegrating tablet. Patients treated with alpha-blockers who have previously used vardenafil film-coated tablets may be changed to vardenafil orally disintegrating tablet at the advice of their healthcare provider. Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including vardenafil orally disintegrating tablet, 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 )] leading to symptomatic hypotension (for example, fainting). Consideration should be given to the following: Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor. Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors. In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest recommended starting dose. In patients taking alpha-blockers, do not initiate vardenafil therapy with vardenafil orally disintegrating tablet. Lower doses of vardenafil film-coated tablets should be used as initial therapy in these patients [see Dosage and Administration ( 2.4 )] . In those patients already taking an optimized dose of PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increases in alpha-blocker dose may be associated with further lowering of blood pressure in patients 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 anti-hypertensive drugs. 5.7 Congenital or Acquired QT Prolongation In a study of the effect of vardenafil on QT interval in 59 healthy males [see Clinical Pharmacology ( 12.2 )] , therapeutic (10 mg film-coated tablets) and supratherapeutic (80 mg) doses of vardenafil and the active control moxifloxacin (400 mg) produced similar increases in QTc interval. A postmarketing study evaluating the effect of combining vardenafil with another drug of comparable QT effect showed an additive QT effect when compared with either drug alone [see Clinical Pharmacology ( 12.2)] . These observations should be considered in clinical decisions when prescribing vardenafil to patients with known history of QT prolongation or patients who are taking medications known to prolong the QT interval. Patients taking Class 1A (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic medications or those with congenital QT prolongation, should avoid using vardenafil orally disintegrating tablet. 5.8 Hepatic Impairment Do not use vardenafil orally disintegrating tablet in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment [see Dosage and Administration ( 2.3) Clinical Pharmacology ( 12.3 )] and Use in Specific Populations (8.6 )] . 5.9 Renal Impairment Do not use vardenafil orally disintegrating tablet in patients on renal dialysis, as vardenafil has not been evaluated in this population [see Dosage and Administration ( 2.3 ) and Use in Specific Populations ( 8.7 )]. 5.10 Combination with Other Erectile Dysfunction Therapies The safety and efficacy of vardenafil orally disintegrating tablet used in combination with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. 5.11 Effects on Bleeding In humans, vardenafil film-coated tablet alone in doses up to 20 mg does not prolong the bleeding time. There is no clinical evidence of any additive prolongation of the bleeding time when vardenafil is administered with aspirin. Vardenafil orally disintegrating tablet has not been administered to patients with bleeding disorders or significant active peptic ulceration. Therefore vardenafil orally disintegrating tablet should be administered to these patients after careful benefit-risk assessment. 5.12 Phenylketonurics Vardenafil orally disintegrating tablet contains aspartame, a source of phenylalanine which may be harmful for people with phenylketonuria. Phenylketonurics: Each vardenafil orally disintegrating tablet contains 3.36 mg phenylalanine per tablet. 5.13 Fructose Intolerance Vardenafil orally disintegrating tablets does not contain Sorbitol. 5.14 Sexually Transmitted Disease The use of vardenafil orally disintegrating tablet offers no protection against sexually transmitted diseases. Counseling of patients about protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), should be considered.
6 ADVERSE REACTIONS The following serious adverse reactions with the use of vardenafil orally disintegrating tablet are discussed elsewhere in the labeling: Cardiovascular effects [see Contraindications ( 4.1 ) and Warnings and Precautions ( 5.1) ] Priapism [see Warnings and Precautions ( 5.3) ] QT Prolongation [see Warnings and Precautions ( 5.7) ] Effects on eye [see Warnings and Precautions ( 5.4 )] Sudden hearing loss [see Warnings and Precautions ( 5.5 )] Adverse reactions reported by ≥ 2% ...
6 ADVERSE REACTIONS The following serious adverse reactions with the use of vardenafil orally disintegrating tablet are discussed elsewhere in the labeling: Cardiovascular effects [see Contraindications ( 4.1 ) and Warnings and Precautions ( 5.1) ] Priapism [see Warnings and Precautions ( 5.3) ] QT Prolongation [see Warnings and Precautions ( 5.7) ] Effects on eye [see Warnings and Precautions ( 5.4 )] Sudden hearing loss [see Warnings and Precautions ( 5.5 )] Adverse reactions reported by ≥ 2% of patients treated with vardenafil orally disintegrating tablet: Headache, flushing, nasal congestion, dyspepsia, dizziness, back pain. ( 6.1 ) 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 [see Warnings and Precautions ( 5.4) and Patient Counseling Information ( 17 )] . 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 [see Patient Counseling Information ( 17 )] .
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.