TRIMAGRA 100 Tablet

For the treatment of erectile dysfunction

Dosage and Administration

The recommended dose is 50mg, taken as needed approximately 1 hour before sexual activity. Based on efficacy and toleration, the dose may be increased to 100mg or decreased to 25mg. The maximum recommended dose is 100mg. The maximum recommended dosing frequency is once per day.

Use in the Elderly and in Patients with Impaired Renal or Hepatic Function

See the package insert about the details.

Use in children

TRIMAGRA is not indicated for use in children.

In patients with known sensitivity to any component of the tablet.

In patients with known hypotension, unstable angina, myocardial infarction, recently stroke, hereditary degenerative retinal disorders.

Consistent with its known effects on the nitric oxide/cGMP pathway. TRIMAGRA was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using organic nitrates either regularly and/or intermittently in any form is therefore contraindicated.

Serious cardiovascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack and hypertension, have been reported post-marketing in temporal association with the use of Sildenafil Citrate. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur shortly after the use of Sildenafil Citrate without sexual activity. Others were reported to have occurred hours to days after the use of Sildenafil Citrate and sexual activity. It is not possible to determine whether these events are related directly to Sildenafil Citrate to sexual activity, to the patient’s underlying cardiovascular disease, to a combination of these factors, or to other factors.

Headache, flushing, dizziness, hypotension, angina pectoris, AV block, migraine, tachycardia, palpitation, hypotension, postural hypotension, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy have also been reported.

In Vitro Studies: Sildenafil is a weak inhibitor of the CYP450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4.Given Sildenafil pea plasma concentrations of approximately 1mcM after recommended doses, it is likely that Sildenafil Citrate will alter the clearance of substrates of these isoenzymes.

In Vivo Studies: When Sildenafil Citrate 100mg oral was coadministered with Amlodipines, 5mg or 10mgoral, to hypertensive patients. The mean additional reduction on supine blood pressure was 8mmHg systolic and 7mmHg diastolic.

No significant interactions were shown with Tolbutamide (250mg) or Warfarin (40mg), both of which are metabolized by CYP2C9.

Sildenafil Citrate (100mg) did not potentiate the increase in bleeding time caused by aspirin (150mg). Sildenafil Citrate (100mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%.

Sildenafil (100mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, Saquinavir and Ritonavir, both of which are CYP3A4 substrates.

TRIMAGRA is not indicated for use in women.

No teratogenic effects, impairment of fertility or adverse effects on peri-postnatal development were found in reproduction studies in rats and rabbits following oral administration of Sildenafil.

Warnings:

There is a potential for cardiac risk of sexual activity in patients with pre-existing cardiovascular disease. Therefore, treatments for erectile dysfunction, including TRIMAGRA, should not be generally used in men for whom sexual activity inadvisable because of their underlying cardiovascular status.

Precautions:

Thorough medical history and physical examination should be under taken to diagnose erectile dysfunction, determine potential underlying causes, and identify appropriate treatment.

TRIMAGRA has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers.

Physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity.

There is 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) or hypertension (BP>170/110);

 Patients with cardiac failure or coronary artery disease causing unstable angina;

 Patients with retinitis pigmnentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

TRIMAGRA is an oral therapy for erectile dysfunction. In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis.

The physiological mechanism responsible for erection of the penis involves the release of nitric oxide in the corpus cavemosum during sexual stimulation. Nitric oxide (NO) then activated the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavemosum and allowing inflow of blood.

Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP. Sildenafil has no direct relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by Sildenafil results in increased corpus cavemosum levels of cGMP. Therefore sexual stimulation is required in order for Sildenafil to produce its intended beneficial pharmacological effects.