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 hydrochloride 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).
Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including vardenafil hydrochloride, 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 to 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 hydrochloride, 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 hydrochloride, for this uncommon condition.
Vardenafil hydrochloride 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.
Physicians should advise patients to stop taking all PDE5 inhibitors, including vardenafil hydrochloride, 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)].
Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including vardenafil hydrochloride, 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 leading to symptomatic hypotension (for example, fainting) [see Drug Interactions (7.1) and Clinical Pharmacology (12.2)]. 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 [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 increase 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.
In a study of the effect of vardenafil hydrochloride on QT interval in 59 healthy males [see Clinical Pharmacology (12.2)] , therapeutic (10 mg) 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 hydrochloride 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 hydrochloride 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 hydrochloride.
Dosage adjustment is necessary in patients with moderate hepatic impairment (Child-Pugh B). Do not use vardenafil hydrochloride in patients with severe (Child-Pugh C) hepatic impairment [see Dosage and Administration (2.3), Clinical Pharmacology (12.3) and Use in Specific Populations (8.6)].
The safety and efficacy of vardenafil hydrochloride used in combination with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.
In humans, vardenafil 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 hydrochloride has not been administered to patients with bleeding disorders or significant active peptic ulceration. Therefore vardenafil hydrochloride should be administered to these patients after careful benefit-risk assessment.
The use of vardenafil hydrochloride 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.
The following serious adverse reactions with the use of vardenafil hydrochloride 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)]
- Effects on Eye [see Warnings and Precautions (5.4)]
- Sudden Hearing Loss [see Warnings and Precautions (5.5)]
- QT Prolongation [see Warnings and Precautions (5.7)]
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