Product Overview
[Drug Name] Generic name: Sildenafil Citrate Tablets
Trade name: AoGe
English name: Sildenafil Citrate Tablets
Chinese Pinyin: JuYuanSuanXiDiNaFeiPian
[Ingredients] The main ingredients of this product are: Sildenafil Citrate, whose chemical name is: 1-{4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonyl}-4-methylpiperazine citrate. Molecular formula: C22H30N6O4S•C6H8O7 Molecular weight: 666.70
[Properties] This product is a film-coated tablet, which is white or off-white after removing the coating.
[Indications] Sildenafil is suitable for the treatment of erectile dysfunction.
[Dosage and Administration] For most patients, the recommended dose is 50 mg, taken as needed approximately 1 hour before sexual activity; however, it can be taken at any time within 0.5 to 4 hours before sexual activity. Based on efficacy and tolerability, the dose can be increased to 100 mg (maximum recommended dose) or reduced to 25 mg. Take up to once a day. In the absence of sexual stimulation, the recommended dose of sildenafil is ineffective. The following factors are associated with increased plasma sildenafil levels (AUC): age over 65 years (increase of 40%), liver damage (such as cirrhosis, increase of 80%), severe renal impairment (creatinine clearance)
[Adverse Reactions]
The following issues are discussed in more detail in other sections of the labeling: • Cardiovascular see WARNINGS - Cardiovascular • Prolonged Erection and Priapism see WARNINGS - Prolonged Erection and Priapism • Effects on Eyes see Patient Information - Effects on Eyes • Hearing Loss see Patient Information - Hearing Loss • Hypotension with Concomitant Use of Alpha-Blockers or Antihypertensives see WARNINGS - Hypotension with Concomitant Use of Alpha-Blockers or Antihypertensives • Adverse Reactions Due to Concomitant Use of Ritonavir see WARNINGS - Adverse Reactions Due to Concomitant Use of Ritonavir • Concomitant Use of Other PDE5 Inhibitors or Other Erectile Dysfunction Therapies see WARNINGS - Concomitant Use of Other PDE5 Inhibitors or Other Erectile Dysfunction Therapies • Effects on Bleeding see WARNINGS - Effects on Bleeding • Patient Counseling Advice Regarding Sexually Transmitted Diseases see Patient Information - Patient Counseling Advice Regarding Sexually Transmitted Diseases The most common adverse reactions (2%) reported in clinical trials included headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, and rash. Pre-marketing experience: Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions observed in clinical trials of one drug cannot be directly compared with the incidence of adverse reactions of another drug in clinical trials, nor can it reflect the incidence observed in clinical practice. In clinical trials worldwide, more than 3,700 patients (aged 19 to 87 years) took sildenafil. More than 550 of these patients were treated for more than one year. In placebo-controlled clinical trials, the discontinuation rate due to adverse reactions in the trial group (2.5%) was not significantly different from that in the placebo group (2.3%). Adverse reactions are generally transient and mostly mild to moderate in nature. In various forms of clinical trials, adverse events reported by patients in the trial group are usually similar. In fixed-dose trials, the incidence of some adverse events increases with increasing doses. Generally, flexible-dose trials better reflect the recommended dose usage of the drug, and the nature of adverse events seen in the trial is similar to that in fixed-dose trials. In fixed-dose trials, the incidence of some adverse reactions increases with increasing doses. Flexible-dose trials more closely reflect the recommended dosing schedule of the drug, and the nature of adverse reactions seen in the trials is similar to that in fixed-dose trials. When doses are taken above the recommended dose range, adverse reactions are similar to those described in Table 1 below, but generally occur more frequently. Table 1. Adverse reactions reported by ≥2% of patients in fixed-dose Phase II/III clinical trials and more often in the trial group than in the placebo group* Visual abnormalities: mild to moderate, transient, mainly manifested as pale vision, but also increased sensitivity to light or blurred vision. In flexible-dose, placebo-controlled clinical trials lasting 2-26 weeks, patients who took sildenafil at least once a week as recommended (on-demand dosing) reported the following adverse reactions: Table 2. Adverse reactions reported by ≥2% of patients in on-demand, flexible-dose Phase II/III clinical trials and more often in the trial group than in the placebo group* Visual abnormalities: mild and transient, mainly manifested as pale vision, but also increased sensitivity to light or blurred vision. In these trials, only one patient discontinued the drug due to visual abnormalities. The following adverse reactions occurred at a rate of 2%, but the incidence was the same in the experimental group and the placebo group. They are: respiratory tract infection, back pain, flu symptoms and joint pain. In the fixed-dose trial, dyspepsia (17%) and visual abnormalities (11%) were more common in the 100 mg dose group than in the lower dose group. When the recommended dose range is exceeded, the adverse events are similar to the previous ones, but the frequency of reporting increases. The following are the incidences in controlled clinical trials.
[Contraindications]
Nitrates: Due to the known effects of sildenafil citrate tablets on the nitric oxide/cGMP pathway (see Pharmacology and Toxicology), sildenafil can enhance the hypotensive effect of nitrates. Therefore, patients taking nitric oxide donors (such as any form of organic nitrates or organic nitrites), whether taking them regularly or intermittently, are contraindicated. PDE5 inhibitors (including sildenafil) are prohibited from being used in combination with guanylate cyclase agonists (such as riociguat) because this may cause symptomatic hypotension. It is not clear when patients can safely take nitrates (if necessary) after taking sildenafil. Based on the pharmacokinetic data of healthy volunteers, a single oral dose of 100 mg resulted in a plasma sildenafil concentration of approximately 2 ng/ml (peak plasma concentration of approximately 440 ng/ml) 24 hours later (see Pharmacokinetics). The plasma sildenafil concentration of the following patients was 3 to 8 times higher than that of healthy volunteers 24 hours after taking the medicine: those over 65 years old, those with liver damage (such as cirrhosis), those with severe renal damage (creatinine clearance below 30ml/min), and those taking strong inhibitors of cytochrome P4503A4 such as erythromycin.Although sildenafil blood concentrations are well below peak concentrations 24 hours after dosing, it is not known whether nitrates can be safely taken at this time. Patients with known hypersensitivity to any of the ingredients in this product are contraindicated. WARNINGS Cardiovascular: Sexual activity is potentially dangerous to the heart in patients with pre-existing cardiovascular disease. Therefore, patients whose cardiovascular status is not suitable for sexual activity should generally not use drugs for the treatment of erectile dysfunction, including sildenafil. Sildenafil causes systemic vasodilation, resulting in a transient decrease in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg) (see Pharmacology and Toxicology).Usually, in most patients, the consequences of this effect can be ignored, but physicians should carefully consider whether this vasodilatory effect will cause adverse consequences in patients with cardiovascular disease before prescribing, especially during sexual activity. Patients with the following underlying diseases may be particularly sensitive to the effects of vasodilators, including sildenafil - including left ventricular outflow tract obstruction (such as aortic stenosis, idiopathic hypertrophic subaortic stenosis) and diseases with severe impairment of autonomic control of blood pressure. Such patients should use the drug with caution. Currently, there are no controlled clinical trial data on the safety and efficacy of sildenafil in the following groups. Prescription should be cautious in such patients: patients who have had myocardial infarction, shock or life-threatening arrhythmias within the past 6 months; patients with resting hypotension (blood pressure below 90/50 mmHg) or hypertension (blood pressure above 170/110 mmHg); patients with unstable angina due to heart failure or coronary artery disease; patients with pigmentary retinitis (a few patients with this disease have inherited abnormalities of retinal phosphodiesterase). People with sickle cell anemia or related anemias.Prolonged erection and abnormal penile erection: After the approval of sildenafil citrate tablets abroad, there have been a small number of reports of prolonged erection (more than 4 hours) and abnormal erection (painful erection for more than 6 hours). If the erection lasts for more than 4 hours, the patient should seek medical attention immediately. If the abnormal erection is not treated immediately, the penile tissue may be damaged and may cause permanent loss of erectile function. Sildenafil should be used with caution in patients with the following diseases: penile anatomical malformations (such as penile deviation, cavernous fibrosis, Peyronie's disease), diseases that are prone to abnormal penile erection (such as sickle cell anemia, multiple myeloma, leukemia). However, there are currently no controlled clinical data on the safety or efficacy of this product in patients with sickle cell anemia or related anemia. Adverse reactions caused by combined use with ritonavir: Taking the protease inhibitor ritonavir at the same time will significantly increase the blood concentration of sildenafil (AUC increased by 11 times). Patients taking ritonavir should use sildenafil with caution. There is limited information on the effects of high blood concentrations of sildenafil on subjects, except that visual abnormalities are more common at high doses. Some healthy subjects taking high doses of sildenafil (200-800 mg) reported decreased blood pressure, syncope, and prolonged erection. To reduce the possibility of adverse events in patients taking ritonavir, it is recommended to reduce their sildenafil dosage.
【Precautions】
General matters When diagnosing erectile dysfunction, its underlying cause should be identified, and appropriate treatment plans should be determined after a comprehensive medical examination. Before using sildenafil on patients, it is important to note the following important issues: Hypotension when used in combination with alpha-blockers or antihypertensive drugs Alpha-blockers: PDE5 (phosphodiesterase type 5) inhibitors should be used with caution when used in combination with alpha-blockers. PDE5 inhibitors (including this product) and alpha-blockers are both vasodilators and have the effect of lowering blood pressure. When vasodilators are used in combination, it can be expected that the effects on blood pressure may be additive. In some patients, the combination of these two types of drugs can significantly lower blood pressure and cause symptoms of hypotension (such as dizziness, lightheadedness, and syncope) (see Drug Interactions). The following situations should also be noted: – Patients should have reached a stable state of alpha-blocker treatment before receiving sildenafil treatment. Patients who take alpha-blockers alone to treat hemodynamic instability are at increased risk of hypotension symptoms after taking PDE5 inhibitors in combination.Patients who have reached a stable state on alpha-blocker therapy should be started on the lowest dose of PDE5 inhibitors. – For patients who are already taking the optimal dose of PDE5 inhibitors, alpha-blocker therapy should be started on the lowest dose. Co-administration of PDE5 inhibitors may further reduce blood pressure as the alpha-blocker dose is gradually increased. – The safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other factors, including insufficient intravascular volume and other antihypertensive drugs. Antihypertensive drugs: Sildenafil dilates systemic blood vessels and may enhance the antihypertensive effect of other antihypertensive drugs. Major clinical trials included patients taking multiple antihypertensive drugs. Another independent drug interaction study showed that when hypertensive patients taking 5mg or 10mg of amlodipine were given 100mg of sildenafil citrate tablets, systolic and diastolic blood pressures were further reduced by an average of 8mmHg and 7mmHg respectively (see Drug Interactions).In three drug interaction studies, patients with benign prostatic hyperplasia (BPH) who were receiving doxazosin therapy to a stable state were concurrently treated with the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, or 100 mg). In these study populations, a further average decrease in supine blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, respectively, and a further average decrease in standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, was observed. If a higher dose of sildenafil is taken concurrently with doxazosin (4 mg), individual patients have reported symptoms of orthostatic hypotension within 1 to 4 hours after taking the drug, including dizziness and lightheadedness, but not syncope. Patients taking alpha-blockers concurrently with sildenafil may cause symptoms of hypotension in some patients.Therefore, if the dose of sildenafil exceeds 25 mg, it should not be taken within 4 hours of taking alpha-blockers. Safety database analysis shows that there is no difference in the side effects of patients taking sildenafil with or without antihypertensive drugs. In post-marketing experience, there are reports of prolonged erections and abnormal erections associated with sildenafil. If the erection lasts for more than 4 hours, the patient should seek medical attention immediately. If the abnormal erection is not treated immediately, the penile tissue may be damaged and may cause permanent loss of erectile function. Combination with other PDE5 inhibitors or other erectile dysfunction treatments: The safety and efficacy of other PDE5 inhibitors, or other pulmonary arterial hypertension (PAH) treatments containing sildenafil (Revatio), or other erectile dysfunction treatments in combination with this product have not been studied. Such combined use may further lower blood pressure. Therefore, combined use is not recommended.Effects on Bleeding: Postmarketing bleeding events have been reported in patients who have taken sildenafil citrate tablets. A causal relationship between this product and these events has not been established. Sildenafil citrate tablets have no effect on human bleeding time, whether used alone or in combination with aspirin. However, in vitro experiments have shown that sildenafil citrate tablets enhance the anti-aggregation effect of sodium nitroprusside (a nitric oxide donor) on human platelets. In addition, in anesthetized rabbits, the combination of heparin and sildenafil has an additive effect on prolonging bleeding time, but similar human studies have not been conducted. The safety of sildenafil citrate tablets in patients with bleeding disorders and active peptic ulcers is currently unknown. Patient Information Physicians should explain to patients that sildenafil is prohibited from being taken simultaneously with nitrates (regularly or intermittently). Physicians should inform patients that sildenafil has the potential to enhance the antihypertensive effect of alpha-blockers and other antihypertensive drugs. Taking sildenafil and alpha-blockers together may cause hypotension symptoms in some patients. When sildenafil and alpha-blockers need to be used concomitantly, patients should have achieved a stable state of alpha-blocker treatment before sildenafil treatment, and sildenafil should be started at the lowest dose.Physicians should explain to patients that sexual activity is potentially dangerous to the heart when cardiovascular risk factors are present. If symptoms such as angina, dizziness, and nausea occur at the beginning of sexual activity, sexual activity should be stopped and these situations should be discussed with the doctor. Effects on the eyes: Physicians should inform patients that if sudden vision loss occurs in one or both eyes, they should immediately stop taking all phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil citrate tablets, and consult a doctor. This situation may be a manifestation of non-arteritic anterior ischemic optic neuropathy (NAION), a disease that can cause vision loss, including permanent loss. Rare reports of NAION related to the duration of medication have been reported in all post-marketing applications of PDE5 inhibitors. An observational case-crossover study evaluated the risk of NAION when using PDE5 inhibitors just before the onset of NAION (within 5 half-lives) compared with the use of PDE5 inhibitors over a period of time. The results showed that the risk of NAION increased by approximately 2 times, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported consistent results with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION (e.g., optic disc “crowding”) may be involved in the NAION that occurred in these studies.Rare post-marketing reports and observational studies of associations between PDE5 inhibitor use and NAION have not demonstrated a causal relationship between PDE5 inhibitor use and NAION (see Adverse Reactions/Post-Marketing Experience). Published literature data show that in the general population, the annual incidence of NAION is 2.5 to 11.8 cases per 100,000 men (≥50 years old). If sudden vision loss occurs, patients should be advised to stop taking sildenafil and consult a physician immediately. For patients with potential NAION risk factors, physicians should consider whether they will be adversely affected by the use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of recurrence of NAION. Physicians should inform patients who have experienced unilateral NAION that they are at increased risk of recurrence of NAION regardless of whether vasodilators such as PDE5 inhibitors will have adverse effects on them. In these patients, PDE5 inhibitors (including sildenafil) should be used with caution only when the expected benefits outweigh the risks.Patients with "crowded" optic discs are also thought to be at higher risk for NAION than the general population, but evidence is insufficient to support screening potential users of PDE5 inhibitors (including this product) for this uncommon condition. There are no controlled clinical data on the safety or efficacy of this product in patients with retinitis pigmentosa (a small number of whom have a genetic disorder of retinal phosphodiesterase). It is not certain that these events are directly related to the use of PDE5 inhibitors or are related to other factors. Physicians should inform patients who have experienced unilateral NAION that they are at increased risk for another NAION regardless of whether vasodilator drugs such as PDE5 inhibitors may have adverse effects on them (see "Adverse Reactions/Postmarketing Experience/Special Sensations").Hearing loss: Doctors should inform patients that if hearing loss or loss occurs suddenly, they should stop taking PDE5 inhibitors (including this product) and seek medical attention as soon as possible. Such events may be accompanied by tinnitus and dizziness, and are reported to be temporally related to the use of PDE5 inhibitors (including sildenafil citrate tablets). However, it is not certain whether such events are directly related to the use of PDE5 inhibitors or other factors (see Adverse Reactions/Pre-Marketing Experience and Post-Marketing Experience). Doctors should warn patients: After the approval of sildenafil citrate tablets abroad, there have been a small number of reports of prolonged erections (more than 4 hours) and abnormal erections (painful erections for more than 6 hours). If the erection lasts for more than 4 hours, the patient should seek medical attention immediately. If abnormal erections are not treated immediately, penile tissue may be damaged and may lead to permanent loss of erectile function. Doctors should inform patients that this product should not be used in combination with other PDE5 inhibitors. The safety and effectiveness of this product in combination with other PDE5 inhibitors have not been studied. Patient Counseling Regarding Sexually Transmitted Diseases: Sildenafil does not protect against sexually transmitted diseases. Patients should be informed of measures to prevent sexually transmitted diseases (including human immunodeficiency virus, HIV), as appropriate. Effects on Ability to Drive and Use Machines Because dizziness and visual changes have been reported in clinical studies of sildenafil, patients should be informed of their possible reactions to sildenafil before driving or operating machines. The effects of sildenafil on the ability to drive and use machines have not been studied.
[Special Population Use] Precautions for Children:
Sildenafil is not suitable for newborns and children.
Precautions for pregnancy and lactation:
Sildenafil is not suitable for pregnant women. There is currently no data on the use of sildenafil by pregnant women to find the risk of adverse developmental outcomes associated with the drug. Animal reproduction studies using sildenafil have shown that when rats and rabbits were given doses of 16 times and 32 times the maximum recommended human dose (MRHD, 100 mg/day, calculated as mg/m2), no adverse developmental outcomes occurred during organogenesis.
Sildenafil is not suitable for lactating women. Limited data indicate that sildenafil and its active metabolites are secreted in human milk. There is currently no information on the effects of such breast milk on children, and the effects of sildenafil on breast milk production.
Precautions for the Elderly:
Sildenafil clearance is reduced in healthy elderly volunteers (≥65 years old) (see "Pharmacokinetics: Pharmacokinetics in Special Populations"). Considering that higher blood drug concentrations may increase both efficacy and the occurrence of adverse events, the starting dose should be 25 mg (see Dosage and Administration).
[Storage] Keep away from light and store in a sealed container
[Specification] 50mg*3 tablets*2 plates
[Validity period] 36 months
[Implementation standard] Implementation standard] WS1-(X-010)-2010Z-2021
[Approval number] National Medicine Standard H20174092
[Manufacturer] Company name: Chengdu Diao Pharmaceutical Group Co., Ltd.
