Dom-Sildenafil Product Monograph

SUMMARY PRODUCT INFORMATION

INDICATIONS AND CLINICAL USE

Dom-SILDENAFIL (sildenafil citrate) is indicated for:

• the treatment of erectile dysfunction, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance.

CONTRAINDICATIONS

Sildenafil citrate has been shown to potentiate the hypotensive effects of nitrates in healthy volunteers and in patients, and is therefore contraindicated in patients who are taking any type of nitrate drug therapy, or who utilize short-acting nitrate-containing medications, due to the risk of developing potentially life-threatening hypotension. The use of organic nitrates, either regularly and/or intermittently, in any form (e.g. oral, sublingual, transdermal, by inhalation) is absolutely contraindicated (see ACTION AND CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION).

After patients have taken sildenafil citrate, it is unknown when nitrates, if necessary, can be safely administered. Plasma levels of sildenafil at 24 hours post-dose are much lower (2 ng/mL) than at peak concentration (440 ng/mL). In the following patients: age >65, hepatic impairment (e.g. cirrhosis), severe renal impairment (e.g. CL_cr <30 mL/min), and concomitant use of potent cytochrome P-450 3A4 inhibitors (erythromycin), plasma levels of sildenafil at 24 hours post- dose have been found to be 3 to 8 times higher than those seen in healthy volunteers. Although plasma levels of sildenafil at 24 hours post-dose are much lower than at peak concentration, it is unknown

whether nitrates can be safely coadministered at this time point (see DETAILED PHARMACOLOGY, Pharmacodynamic Studies).

Treatments for erectile dysfunction should not be generally used in men for whom sexual activity is inadvisable (see also WARNINGS AND PRECAUTIONS).

Dom-SILDENAFIL is contraindicated in patients with a known hypersensitivity to any component of the tablet (see PHARMACEUTICAL INFORMATION).

WARNINGS AND PRECAUTIONS

General

The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment.

Cardiovascular

As with all treatments for erectile dysfunction, there is a potential cardiac risk of sexual activity in patients with pre-existing cardiovascular disease, including hypertension (BP>140/90). Therefore, treatments for erectile dysfunction, including sildenafil citrate, should not be generally administered in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.

There are no controlled clinical data on the safety or efficacy of sildenafil citrate in the following groups, if prescribed, this should be done with caution.

• Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months
• Patients with resting hypotension (BP <90/50 at rest) or hypertension (BP >170/110 at rest)

• Patients with cardiac failure or coronary artery disease causing unstable angina (see

  ACTION AND CLINICAL PHARMACOLOGY).

Caution is advised when sildenafil is administered to patients taking an alpha-blocker, as the coadministration may lead to symptomatic hypotension in a few susceptible individuals (see DRUG INTERACTIONS). In order to minimize the potential for developing postural hypotension, patients should be hemodynamically stable on alpha-blocker therapy prior to initiating sildenafil treatment. Initiation of sildenafil at lower doses should be considered. In addition, physicians should advise patients what to do in the event of postural hypotensive symptoms.

Hematologic

In clinical trials, sildenafil has been shown to have systemic vasodilatory properties that result in transient decreases in blood pressure (see DETAILED PHARMACOLOGY). This is of little or no consequence in most patients. However, prior to prescribing sildenafil, physicians should carefully consider whether their patients with certain underlying conditions could be adversely affected by such vasodilatory effects, especially in combination with sexual activity. Patients with increased susceptibility to vasodilators include those with left ventricular outflow obstruction (e.g.,

aortic stenosis, hypertrophic obstructive cardiomyopathy), or those with the rare syndrome of multiple system atrophy manifesting as severely impaired autonomic control of blood pressure.

In humans, sildenafil citrate has no effect on bleeding time when taken alone or with acetylsalicylic acid. In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). The combination of heparin and sildenafil citrate had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans (see ACTION AND CLINICAL PHARMACOLOGY).

There is no safety information on the administration of sildenafil citrate to patients with bleeding disorders or active peptic ulceration. Therefore, sildenafil citrate should be administered with caution to these patients.

Hepatic/Biliary/Pancreatic

In volunteers with hepatic cirrhosis (Child-Pugh A and B), sildenafil clearance was reduced, resulting in increases in AUC (84%) and C_max (47%) compared to age-matched volunteers with no hepatic impairment.

A starting dose of 25 mg should be considered in patients with hepatic impairment (see ACTION AND CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION).

Ophthalmologic

Postmarketing reports of sudden loss of vision have occurred rarely, in temporal association with the use of PDE5 inhibitors. It is not clear whether these are related directly to the use of PDE5 inhibitors or to other factors. There may be an increased risk to patients who have already experienced Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION).

There are no controlled clinical data on the safety or efficacy of sildenafil citrate in patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases). If prescribed, this should be done with caution. (see ACTION AND CLINICAL PHARMACOLOGY).

A small percentage of patients experience visual effects (e.g. impairment of colour discrimination, increased perception to light, blurred vision, eye pain, ocular redness) after taking sildenafil citrate. If this happens, then the patient should not operate a motor vehicle or any heavy machinery until the adverse effects disappear (see ACTION AND CLINICAL PHARMACOLOGY).

Rare cases of central serous chorioretinopathy have been reported during the post-marketing period in temporal association with the use of sildenafil citrate. It is not known if medical and other facts were reported that may have also played a role in the development of the condition. It is not possible to determine whether the development of the condition was related directly to the use of sildenafil, to the patient’s possible underlying risk factors, a combination of these factors, or to other factors. These cases of central serous chorioretinopathy in patients receiving sildenafil did not provide evidence of serious or permanent alteration in visual function. (See POST-MARKET ADVERSE DRUG REACTIONS).