Viagra in the Management
of Erectile Dysfunction

Management of Erectile Dysfunction (ED)
 I. Erectile Dysfunction: Definition
   Definition and Epidemiology of Erectile Dysfunction
 II. VIAGRA: Clinical Efficacy
   General Assessments of Efficacy
   Major Clinical Trials
   Efficacy in Special Populations
 III. VIAGRA: Safety
   Safety Overview
   Adverse Events  & Discontinuations
   Contraindications & Precautions
 IV. VIAGRA: Pharmacokinetics & Pharmacodynamics
   Interactions
 V. Mechanism of Action
 VI. Dosage and Administration
 VII. Conclusions

Erectile Dysfunction
Definition
Erectile dysfunction (ED) is defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual activity

Erectile Dysfunction
Etiology
ED can be classified as
organic: due to vasculogenic, neurologic, hormonal, or cavernosal abnormalities or lesions
psychogenic: due to central inhibition of the erectile mechanism without a physical insult
mixed organic/psychogenic: due to a combination of organic and psychogenic factors.

Erectile Dysfunction
Associated Risk Factors
Chronic illnesses
Surgery and trauma
Pharmacotherapy
Lifestyle factors

Erectile Dysfunction
Associated Risk Factors
Chronic Illnesses
Systemic diseases: atherosclerosis, diabetes mellitus, cardiovascular disease, renal failure, hepatic failure
Neurogenic diseases: Alzheimer’s disease, multiple sclerosis
Penile disorders: Peyronie’s disease
Psychiatric disorders: depression
Endocrine disorders: hyperthyroidism, hypothyroidism, hypogonadism, hyperprolactinemia

Erectile Dysfunction
Associated Risk Factors
Surgery and Trauma
Neurologic: spinal cord injury1
Pelvic: injury, surgery, and irradiation of the pelvic region2
Urologic: prostatectomy2

Erectile Dysfunction
Associated Risk Factors
Drugs and Other Modifiable Factors1,2
Alcohol abuse
Cigarette smoking
Drugs, including some from the following classes:
Antihypertensives
Antidepressants
Hormones
Tranquilizers
Miscellaneous

Mechanism of Action in Corpus Cavernosal Smooth Muscle Cells
Penile Erection
Nitric Oxide-cGMP Mechanism1

Treatment of Erectile Dysfunction Suggested Characteristics of an Ideal Therapy1
Simple
Non-invasive
Non-painful
High success rate
Few minor side effects

VIAGRA
Convenient oral formulation
Effective
Reliable
Natural - works only in
response to sexual stimulation
Well tolerated
Fast acting, remains active
Suitable for a wide range of patients
 
 

Contraindications
Administration of VIAGRA to patients who use nitric oxide donors or nitrates in any form is contraindicated. Consistent with its known effects on the nitric oxide/cGMP pathway, VIAGRA has been shown to potentiate the hypotensive effects of nitrates.
Also contraindicated in patients with known hypersensitivity to any component of the tablet.

Precautions
Patients with
anatomical deformation of the penis
conditions that may predispose them to priapism
bleeding disorders or active peptic ulceration
with retinitis pigmentosa
Patients for whom sexual activity is inadvisable
The use of combinations of VIAGRA and other treatments for ED have not been studied and are not recommended
 

VIAGRA Was Administered With
the Following Medications
Clinical Trials
Antibiotics/Antifungals
Erythromycin
Ketoconazole
Rifampicin
Anticoagulants
Warfarin
VIAGRA Was Administered With
the Following Medications
Interaction Studies

Dosing & Administration
Recommended dose is 50 mg taken as needed approximately 60 minutes before sexual activity.
Based on efficacy and toleration, the dose may be increased to 100 mg or decreased to 25 mg.
Erectile Dysfunction
Conclusions
Erectile dysfunction is a common condition.
The nitric oxide-cGMP mechanism plays a predominant role in mediating corpus cavernosal smooth muscle relaxation and penile erection.
Erectile dysfunction is associated with age but is not an inevitable consequence of aging.
In addition to age, risk factors include chronic illnesses, pelvic trauma/surgery, some medications, cigarette smoking, and alcohol abuse.

Safety Summary
In clinical trials:
Adverse events (AEs) associated with VIAGRA were transient and mild-to-moderate
Headache (15.8%), flushing (10.5%), dyspepsia (6.5%), and nasal congestion (4.2%) were most frequently reported AEs.
Discontinuation rates due to AEs were comparable for VIAGRA-treated and placebo-treated patients (2.6% and 2.3%, respectively)
No cases of priapism were reported.
VIAGRA is contraindicated in patients who take nitric oxide donors or nitrates in any form.

Summary of Death Reports (130 patients)
 48 - Cause of death unknown or unmentioned
   3 - Stroke
   1 - Drowning
   1 - Homicide
 77 - Cardiac events
 Definite or suspected MI:  41
 Cardiac arrest:    27
 Cardiac symptoms:       6
 Coronary artery disease:    3
Summary of Death Reports (con’t)
 Age (known in 104 patients):
 Median: 64 years
 Range: 27 to 87 years
 Risk factors for CAD (n=90; 70%)
 HTN, hypercholesterolemia, smoking, DM, obesity, previous cardiac history
 On nitrates:  19 (16 confirmed users)
 No previous hx of CAD:  12
 With autopsy: 3 (all with severe CAD)

Summary of Death Reports (con’t)
 Time of death after Viagra (n=128):
 44 (34%)  - Within 4-5 hrs
 27  - During or immediately after sex
 6  - Same day
 8  - Next day
 5  - 2 days later
 4  - 3 to 7 days later
 61 (48%)  - Unknown

FDA Position
FDA will continue to monitor reports
Current reports have not changed FDA’s perspective concerning the safety of ViagraTM
Morbidity and Mortality Reported
 Number of male US deaths due to cardiac diseases according to AHA =
 185-275 deaths/month/million
 Statistics from American Heart Association
 Study on reported ischemic and atherosclerotic heart disease death in Los Angeles County:
 124 deaths/million/month
 Kloner RA, et al., JACC 1997; 30:1174-1180