[Posted 10/18/2007] FDA informed healthcare professionals of reports of sudden decreases or loss of hearing following the use of PDE5 inhibitors sildenafil (Viagra), tadalafil (Levitra), vardenafil (Cialis) for the treatment of erectile dysfunction, and sildenafil (Revatio) for the treatment of pulmonary arterial hypertension. In some cases, the sudden hearing loss was accompanied by tinnitus and dizziness. Medical follow-up on these reports was often limited which makes it difficult to determine if the loss of hearing was related to the use of one of the drugs, an underlying medical condition or other risk factors for hearing loss, a combination of these factors or other factors. The PRECAUTIONS and ADVERSE REACTIONS sections of the approved product labeling for sildenafil (Viagra), tadalafil, and vardenafil were revised. FDA is working with the manufacturer to revise the labeling for sildenafil (Revatio). For more information visit the FDA website at: [Web], [Web] and [Web].
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Erectile Dysfunction
To facilitate attainment of a sexually functional erection in males with erectile dysfunction (ED, impotence).
Dosage and Administration
General
Dosage must be individualized carefully according to the patient’s tolerance and erectile response.
Sexual stimulation is required for response to therapy.
Administration
Oral Administration
Administer orally, no more than once daily, without regard to meals.
Administer approximately 1 hour before anticipated sexual activity.
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Available as vardenafil hydrochloride; dosage expressed in terms of vardenafil.
Adults
Erectile Dysfunction
Oral
Initially, 10 mg. Depending on effectiveness and tolerance, increase dosage to a maximum of 20 mg or decrease to 5 mg. Administer no more frequently than once daily.
Prescribing Limits
Adults
Erectile Dysfunction
Oral
Maximum 20 mg daily.
Special Populations
Hepatic Impairment
In patients with moderate hepatic impairment (Child-Pugh class B), decrease initial dosage to 5 mg; maximum dosage is 10 mg once daily. Not studied in patients with severe hepatic impairment (Child-Pugh class C).
Renal Impairment
Dosage adjustments not required in patients with patients with mild (Clcr of 50–80 mL/minute) to severe (Clcr <30 mL/minute) renal impairment. Not studied in patients requiring renal dialysis.
Geriatric Patients
Reduce initial dose to 5 mg given no more frequently than once daily in men ≥65 years of age.
Cautions
Contraindications
Known hypersensitivity to vardenafil or any ingredient in the formulation.
Concomitant use of nitrates, nitrites, or nitric oxide donors, either regularly or intermittently, or α-adrenergic blocking agents.
Should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.
Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Use not recommended in patients with a recent (within 6 months) MI, stroke, or life-threatening arrhythmia; resting hypotension (<90 mm Hg resting SBP) or hypertension (170/110 mm Hg SBP/DBP); or severe heart failure or unstable angina.
Possible hypotension; consider whether patients with underlying cardiovascular disease could be affected adversely by vardenafil’s vasodilatory activity. Risk of an undesired hypotensive or vasodilatory response is of particular concern in patients with left-ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis).
Potentiation of hypotensive effect with organic nitrates may result in life-threatening hypotension and/or hemodynamic compromise. Possible significant hypotension when given concurrently with α-adrenergic blocking agents. Manufacturers state that concomitant use of nitrates or α-adrenergic blocking agents with vardenafil is contraindicated. (See Specific Drugs under Interactions.)
Safety not established with long-term use of vardenafil concomitantly with potent CYP3A4 inhibitors (e.g., ritonavir, indinavir, ketoconazole, itraconazole). Increased plasma vardenafil concentrations with concomitant use; dosage reduction of vardenafil recommended. (See Specific Drugs under Interactions.)
Priapism
Possible prolonged erections (>4 hours in duration) and priapism (painful erection >6 hours).
May result in penile tissue damage and permanent loss of potency if priapism is not treated immediately. Use with caution in patients with conditions that may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia).
Ocular Effects
Possible visual disturbances (e.g., abnormal, dim, or blurred vision; changes in color vision [e.g., chromatopsia]).
Not studied in patients with hereditary degenerative retinal disorders, including those with retinitis pigmentosa. Use not recommended until further information is available.
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Patient Assessment
Thorough medical history and physical examination recommended to diagnose erectile dysfunction, determine potential underlying causes, and identify appropriate treatment.
Review of the patient’s current drug regimens recommended to detect possible drug-induced erectile dysfunction.
Hematologic Effects
No prolongation of bleeding time with vardenafil dosages ≤20 mg.
However, not studied in patients with bleeding disorders or active peptic ulcers; therefore, careful risk/benefit assessment is necessary before use in such patients.
GU Effects
Use with caution in patients with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie’s disease).
Specific Populations
Pregnancy
Category B. Not indicated for use in women.
Lactation
Not indicated for use in women.
Pediatric Use
Not indicated for use in neonates or children.
Geriatric Use
Safety and efficacy in males ≥65 years of age similar to that in younger males. Increased plasma vardenafil concentrations in men ≥65 years of age compared to that in younger males; therefore consider lower initial dosage. (See Geriatric Patients under Dosage and Administration.)
Hepatic Impairment
Decreased clearance in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. (See Hepatic Impairment under Dosage and Administration.) Not studied in patients with severe hepatic impairment (Child-Pugh class C), and use of the drug in such patients is not recommended.
Renal Impairment
Clearance decreased in patients with moderate (Clcr 30–50 mL/minute) to severe (Clcr <30 mL/minute) renal impairment. (See Renal Impairment under Dosage and Administration.) Not studied in patients with end-stage renal disease requiring dialysis.
Nelfinavir, indinavir, amprenavir, saquinavir, fosamprenavir, or atazanavir: Use initial vardenafil dosage of 2.5 mg and do not exceed a single dose of 2.5 mg in 24 hours
Pharmacokinetic and pharmacodynamic interaction unlikely
Pharmacokinetics
Absorption
Bioavailability
Rapidly absorbed following oral administration; peak concentrations usually attained within 0.5–2 hours.
Absolute bioavailability is approximately 15%.
Food
Administration with a high-fat meal reduces the peak plasma concentrations by 18–50%.
Distribution
Extent
Extensively distributed into tissues.
Plasma Protein Binding
Approximately 95% for the drug and major metabolite.
Elimination
Metabolism
Metabolized in the liver to active metabolite(s) principally via CYP3A4, with minor contributions from CYP3A5 and CYP2C.
Elimination Route
Excreted as metabolites principally in the feces (91–95%) and to a lesser extent in urine (2–6%).
Half-life
Terminal half-life 4–5 hours for drug and major metabolite.
Special Populations
Clearance reduced in men ≥65 years of age, resulting in an increase in AUC and peak plasma concentrations compared with younger males.
Clearance reduced in patients with moderate (Clcr of 30–50 mL/minute) or severe (Clcr <30 ml/minute) renal impairment, resulting in an increase in AUC compared with patients with normal renal function.
Clearance reduced in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, resulting in an increase in AUC and peak plasma concentrations compared with healthy adults.
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C).
Actions
Selective inhibitor of phosphodiesterases (PDEs) with the greatest selectivity for PDE type 5, the principal isoenzyme involved in the metabolism of cGMP to GMP in the corpora cavernosa of the penis.
Enhances the effect of nitric oxide by inhibiting PDE type 5-mediated hydrolysis of cGMP.
Potentiates accumulation of cGMP only when cGMP production in the penis is increased by sexual arousal. No effect on erectile function in the absence of sexual stimulation.
Modest peripheral vasodilation accompanied by a small increase in heart rate at usual dosages.
Although less affinity than sildenafil for PDE type 6 receptor in the retina, some transient visual abnormalities observed.
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Importance of informing patients of the potential for life-threatening hypotension and/or hemodynamic compromise with concurrent use of organic nitrates and nitrites (e.g., nitroglycerin, isosorbide dinitrate) or nitric oxide donors (e.g., sodium nitroprusside) in any form, including the recreational use of inhaled nitrites (“poppers”), because of the potential for hypotension and associated dizziness, syncope, or even MI or stroke.
Importance of avoiding concurrent use of α-adrenergic blocking agents because of the potential for hypotension, dizziness, or fainting.
Importance of seeking immediate medical attention if an erection persists >4 hours or is painful.
Importance of advising patient that vardenafil does not protect against sexually transmitted diseases (e.g., HIV) and about measures to protect against such transmission.
Importance of contacting a clinician for assessment of therapeutic benefit, the need for possible dosage adjustment, and potential adverse effects.
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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