4 CONTRAINDICATIONS

There were four subjects with a decrease

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Two were discontinued after study period 1: one failed to meet pre-dose screening qualifications and the other experienced symptomatic hypotension as a moderately severe adverse event 30 minutes after dosing with open-label sildenafil tablets 50 mg. Of the twenty subjects who were ultimately assigned to treatment, a total of 13 subjects successfully completed dose period 1, and seven had successfully completed the previous doxazosin study (using sildenafil tablets 50 mg). For the 20 subjects who received sildenafil tablets 100 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 100 mg sildenafil tablets or matching placebo are shown in Figure 4. Figure 4: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured after administration of sildenafil tablets at the same times as those specified for the previous doxazosin studies. All three were taking sildenafil tablets 100 mg, and all three reported mild adverse events at the time of reductions in standing SBP, including vasodilation and lightheadedness. from baseline in standing systolic BP >

30 mmHg following sildenafil tablets 100 mg,

one subject with a decrease from baseline in

Quality assurance & global standards for sildenafil 200mg export orders

Sildenafil tablet, USP is formulated as white, film-coated round-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. Binding Characteristics Studies in vitrohave shown that sildenafil is selective for PDE5. This lower selectivity is thought to be the basis for abnormalities related to color vision [see Clinical Pharmacology (12.2)]. In addition to human corpus cavernosum smooth muscle, PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle.

What Is the Maximum Safe Sildenafil Dosage?

The inhibition of PDE5 in some of these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of NO observed in vitro, an inhibition of platelet thrombus formation in vivoand peripheral arterial-venous dilatation in vivo. Effects of Sildenafil Tablets on Erectile Response:In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan®), after sildenafil tablets administration compared with placebo. Most studies assessed the efficacy of sildenafil tablets approximately 60 minutes post dose. The erectile response, as assessed sildenafil citrate chewable tablets by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration. Effects of Sildenafil Tablets on Blood Pressure:Single oral doses of sildenafil (100 mg) administered to healthy volunteers produced decreases in sitting blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8.3/5.3 mmHg).

Does sildenafil interact with other medicines (drug interactions)?

The decrease in sitting blood pressure was most notable approximately 1 to 2 hours after dosing, and was not different than placebo at 8 hours. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg of sildenafil tablets, therefore the effects are not related to dose or plasma levels within this dosage range. Larger effects were recorded among patients receiving concomitant nitrates [see Contraindications (4.1)]. Figure 1: Mean Change from Baseline in Sitting Systolic Blood Pressure, Healthy Volunteers. Effects of Sildenafil Tablets on Blood Pressure When Nitroglycerin is Subsequently Administered: Based on the pharmacokinetic profile of a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL). standing systolic BP > 30 mmHg following

Medical Alternatives and Supplements

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 co-administered at this time point [see Contraindications (4.1)]. Effects of Sildenafil Tablets on Blood Pressure When Co-administered with Alpha-Blockers: Three double-blind, placebo-controlled, randomized, two-way crossover studies were conducted to assess the interaction of sildenafil tablets with doxazosin, an alpha-adrenergic blocking agent. Study 1: Sildenafil tablets with Doxazosin In the first study, a single oral dose of sildenafil tablets 100 mg or matching placebo was administered in a 2-period crossover design to 4 generally healthy males with benign prostatic hyperplasia (BPH). Following at least 14 consecutive daily doses of doxazosin, sildenafil tablets 100 mg or matching placebo was administered simultaneously with doxazosin. Following a review of the data from these first 4 subjects (details provided below), the sildenafil tablets dose was reduced to 25 mg.

Missed Dose

Thereafter, 17 subjects were treated with sildenafil tablets 25 mg or matching placebo in combination with doxazosin 4 mg (15 subjects) or doxazosin 8 mg (2 subjects). The mean subject age was 66.5 years. For the 17 subjects who received sildenafil tablets 25 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 25 mg sildenafil tablets or matching placebo are shown in Figure 2. Figure 2: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours after sildenafil tablets or matching placebo. There were no subjects treated with sildenafil tablets 25 mg who had a standing SBP < 85mmHg.

Tadalafil (Generic Cialis)

There were three subjects with a decrease from baseline in standing systolic BP >30mmHg following sildenafil tablets 25 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and two subjects with a decrease from baseline in standing systolic BP > 30 mmHg following both sildenafil tablets and placebo. Of the four subjects who received sildenafil tablets 100 mg in the first part of this study, a severe adverse event related to blood pressure effect was reported in one patient (postural hypotension that began 35 minutes after dosing with sildenafil tablets with symptoms lasting for 8 hours), and mild adverse events potentially related to blood pressure effects were reported in two others sildenafil citrate tablets 50mg (dizziness, headache and fatigue at 1 hour after dosing; and dizziness, lightheadedness and nausea at 4 hours after dosing). There were no reports of syncope among these patients. For these four subjects, the placebo-subtracted mean maximum decreases from baseline in supine and standing systolic blood pressures were 14.8 mmHg and 21.5 mmHg, respectively. Both of these subjects were protocol violators, one due to a low baseline standing SBP, and the other due to baseline orthostatic hypotension. placebo and one subject with a decrease

from baseline in standing systolic BP >

• The effects of sildenafil 200 mg typically last for 4-6 hours.
• Do not take more than a prescribed dose to avoid overdose symptoms.
• Sildenafil's effectiveness varies based on individual health factors.
• It is available by prescription or from authorized pharmacies.
• The medication can cause priapism, a painful, persistent erection.
• Always follow dosing instructions to ensure safety and efficacy.

30 mmHg following both

• Sildenafil 200 mg is usually prescribed when lower doses do not work.
• The medication is effective only with sexual arousal.
• Use with caution if you have a history of priapism.
• Report any allergies or adverse reactions to your healthcare provider.
• Combining sildenafil with certain antibiotics may increase side effects.
• Regular use may require dose adjustments under medical supervision.

sildenafil tablets and placebo.

7.2 Alpha-blockers

Study 2: Sildenafil tablets with Doxazosin In the second study, a single oral dose of sildenafil tablets 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH. Following at least 14 consecutive days of doxazosin, sildenafil tablets 50 mg or matching placebo was administered simultaneously with doxazosin 4 mg (17 subjects) or with doxazosin 8 mg (3 subjects). The mean subject age in this study was 63.9 years. Twenty subjects received sildenafil tablets 50 mg, but only 19 subjects received matching placebo. One patient discontinued the study prematurely due to an adverse event of hypotension following dosing with sildenafil tablets 50 mg.

8.1 Pregnancy: Teratogenic effects

This patient had been taking minoxidil, a potent vasodilator, during the study. For the 19 subjects who received both sildenafil tablets and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 50 mg sildenafil tablets or matching placebo are shown in Figure 3. Figure 3: Mean Standing Systolic Blood Pressure Change from Baseline Blood pressure was measured after administration of sildenafil tablets at the same times as those specified for the first doxazosin study. In these two subjects, hypotension was reported as a moderately severe adverse event, beginning at approximately 1 hour after administration of sildenafil tablets 50 mg and resolving after approximately 7.5 hours. There was one subject with a decrease from baseline in standing systolic BP >30mmHg following sildenafil tablets 50 mg and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both sildenafil tablets 50 mg and placebo.

Adverse Reactions/Side Effects

Study 3: Sildenafil tablets with Doxazosin In the third study, a single oral dose of sildenafil tablets 100 mg or matching placebo was administered in a 3-period crossover design to 20 generally healthy males with BPH. In dose period 1, subjects were administered open-label doxazosin and a single dose of sildenafil tablets 50 mg simultaneously, after at least 14 consecutive days of doxazosin. Subjects who had successfully completed the previous doxazosin interaction study (using sildenafil tablets 50 mg), including no sildenafil premature ejaculation significant hemodynamic adverse events, were allowed to skip dose period 1. Thereafter, sildenafil tablets 100 mg or matching placebo was administered simultaneously with doxazosin 4 mg (14 subjects) or doxazosin 8 mg (6 subjects) in standard crossover fashion. The mean subject age in this study was 66.4 years.