MEGRA-100 Tablet

For the treatment of erectile dysfunction.

Dosage and administration

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

Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil citrate 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 contraindicated.

Body as a Whole: Face edema, photosensitivity reaction, shock asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury.

Cardiovascular: Angina pectoris, AV block migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, and cardiomyopathy.

Digestive: Vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, abnormal liver function tests, rectal hemorrhage, gingivitis.

Hemic and Lymphatic: Anemia and leukopenia.

Metabolic and Nutritional: Thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hyperesthesia.

Nervous: Ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased hypoesthesia.

Respiratory: Asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum, increased cough.

Skin and Appendages: Urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.

Special Senses: Mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, deafness, ear pain, eye hemorrhage, cataract, dry eyes.

Urogenital: Cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema, anorgasmia.

See the package insert about the details below.

Nitrates

Alpha-blockers

Amlodipine

MEGRA-100 is not indicated for use in newborns, children, or women.

Geriatric Use: Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil. Since higher plasma levels may increase both the efficacy and incidence of adverse events, a starting dose of 25mg should be considered.

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

Sildenafil has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers. While this normally would be expected to be of little consequence in most patients, prior to prescribing Sildenafil, 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.

Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators including Sildenafil - those with left ventricular outflow obstruction (e.g. aortic stenosis, idiopathic hypertrophic sub aortic stenosis) and those with severely impaired autonomic control of blood pressure.

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.

Before prescribing Sildenafil, it is important to note the following:

Caution is advised when Phosphodiesterase Type5 (PDE5) inhibitors are co-administered with alpha-blockers, PDE5 inhibitors, including Sildenafil 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 (e.g. dizziness, lightheadedness, fainting).

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 dose.

- In those patients already taking an optimized dose of a 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 when 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.

MEGRA-100 has systemic vasodilatory properties and may augment the blood pressure lowering effect of other anti-hypertensive medications.

Patients on multiple antihypertensive medications were included in the pivotal clinical trials for. In a separate drug interaction study, when amlodipine, 5mg or 10mg, and MEGRA-100, were orally administered concomitantly to hypertensive patients mean additional blood pressure reduction of 8mmHg systolic and 7mmHg diastolic were noted.

The safety of MEGRA-100 is unknown in patients with bleeding disorder and patients with active peptic ulceration.

MEGRA-100 should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis of Peyronie’s disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).

The safety and efficacy of combinations of MEGRA-100 with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. In humans, MEGRA-100 has no effect on bleeding time when taken alone or with aspirin. 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 MEGRA-100 had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans.

The mechanism of action of Sildenafil citrate involves the release of nitric oxide (NO) in the corpus cavernosum of the penis. NO binds to the receptors of the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation (vasodilation) of the initial cushions of the helicine arteries, resulting in increased inflow of blood and an erection. Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum.