Product Overview
[Drug name]
Generic name: Sildenafil citrate tablets
Trade name: LangMei Sildenafil citrate tablets 100mg*5 tablets
Pinyin full code: LangMei GouYuanSuanXiDiNaFeiPian 100mg*5Pian
[Main ingredients]
The main ingredient of this product is sildenafil citrate. Chemical name: 1-{4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1hydro-pyrazolo[4,3d]pyrimidin-5-yl)benzenesulfonyl}-4-methylpiperazine
Citrate. Molecular formula: C22H30N6O4SxC6H8O7Molecular weight: 666.70
[Properties]
This product is a white or off-white film-coated tablet, which is white or off-white after removing the coating.
[Indications/Main Functions]
Sildenafil is suitable for the treatment of erectile dysfunction.
[Specifications]
100mg*5 tablets
[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 0.54 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 65 years or older (increase of 40%), liver damage (such as cirrhosis, increase of 80%), severe renal impairment (creatinine clearance <30 ml/min, increase of 100%), and concurrent use of potent cytochrome P4503A4 inhibitors (ketoconazole, itraconazole (increase of 200%), erythromycin (increase of 182%), saquinavir (increase of 210%)]. Since higher plasma levels may increase both efficacy and the incidence of adverse events, the starting dose for these patients is 25 mg. A study in healthy subjects without HIV infection Studies have shown that ritonavir can significantly increase the blood level of sildenafil (AUC increased by 11 times, see [Drug Interactions]). In view of this, it is recommended that patients taking ritonavir at the same time should not take more than 2smg per 48 hours. Sildenafil can enhance the antihypertensive effect of nitrates, so patients taking any dosage form of nitric oxide donors and nitrates are prohibited from taking sildenafil. When sildenafil needs to be used in combination with alpha-blockers, the patient has already achieved a stable state with alpha-blocker treatment before sildenafil treatment, and sildenafil should be started at the lowest dose (see [Drug Interactions]).
[Adverse Reactions]
See instructions for details.
[Contraindications]
Nitrates: Due to the known effects of sildenafil citrate 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 following patients had plasma sildenafil concentrations 3 to 8 times higher than that of healthy volunteers 24 hours after taking the drug: those aged 65 years or above, those with liver damage (such as cirrhosis), those with severe renal damage (creatinine clearance below 30 ml/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. Warning 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 erectile dysfunction, including sildenafil. Sildenafil causes a transient decrease in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg) due to systemic vasodilation (see Pharmacology and Toxicology). Usually, in most patients, the consequences of this effect can be ignored, but physicians should still carefully consider whether this vasodilation 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. The drug should be used with caution in such patients.Currently, there is no clinical controlled trial data on the safety and efficacy of sildenafil in the following populations. Prescriptions should be used with caution in such patients: patients who have had myocardial infarction, shock, or life-threatening arrhythmias within the last 6 months; patients with resting hypotension (blood pressure below 90/50 mmHg) or hypertension (blood pressure above 170/110 mmHg); patients with heart failure or unstable angina due to coronary heart disease; patients with pigmentary retinitis (a few patients with this disease have hereditary abnormalities of retinal phosphodiesterase). Patients with sickle cell anemia or related anemia. Prolonged erection and abnormal penile erection: After the approval of sildenafil citrate tablets for marketing 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 abnormal erection is not treated immediately, penile tissue may be damaged and permanent loss of erectile function may occur.Sildenafil should be used with caution in patients with the following diseases: penile anatomical deformities (such as penile deviation, cavernous fibrosis, Peyronie's disease), diseases that are prone to cause abnormal penile erections (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 co-administration with ritonavir: Taking the protease inhibitor ritonavir at the same time will significantly increase the blood concentration of sildenafil (AUC increased by 11 times). Sildenafil should be used with caution in patients taking ritonavir. There is limited information on the effects of high blood concentrations of sildenafil on subjects, and it is only known 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 dose of sildenafil.
【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 fainting) (see [Drug Interactions]).The following should also be noted: - Patients should have reached a stable state on alpha-blocker therapy before receiving sildenafil treatment. Patients who are taking alpha-blockers alone for hemodynamic instability are at increased risk of developing hypotensive symptoms after taking PDE5 inhibitors. - Patients who have reached a stable state on alpha-blocker therapy should start taking PDE5 inhibitors at the lowest dose. - For patients who are already taking the ideal dose of PDE5 inhibitors, alpha-blocker therapy should be started at the lowest dose. Taking PDE5 inhibitors at the same time may further lower blood pressure as the dose of alpha-blockers 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. Patients who were taking multiple antihypertensive drugs at the same time were included in the main clinical trials. Another independent drug interaction study showed that when hypertensive patients taking 5mg or 10mg amlodipine added 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 treatment and reached a stable state took the alpha-blocker doxazosin (4mg and 8mg) and sildenafil (25mg, 50mg or 100mg) at the same time. In these study populations, supine blood pressure was observed to be further reduced by an average of 7/7mmHg, 9/5mmHg and 8/4mmHg, respectively, while standing blood pressure was further reduced by an average of 6/6mmHg, 11/4mmHg and 4/5mmHg respectively.If a higher dose of sildenafil is taken at the same time as doxazosin (4 mg), individual patients have reported symptoms of postural hypotension within 1 to 4 hours after taking the drug, including dizziness and lightheadedness, but without syncope. Patients treated with alpha-blockers taking sildenafil at the same time may cause symptoms of hypotension in some patients. Therefore, sildenafil doses exceeding 25 mg should not be taken within 4 hours of taking alpha-blockers. Safety database analysis shows that there is no difference in side effects in patients taking sildenafil with or without antihypertensive drugs.In post-marketing experience, there have been reports of prolonged erections and abnormal erections associated with sildenafil. If an 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 permanent loss of erectile function may occur. 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 combined with this product have not been studied. Such combined use may further lower blood pressure. Therefore, combined use is not recommended.Effect on bleeding: Post-marketing bleeding events have been reported in patients who have taken sildenafil citrate tablets. The 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 in vitro experiments, sildenafil citrate tablets enhance the anti-aggregation effect of sodium nitroprusside (a nitric oxide donor) on human platelets. In addition, in anesthetized domestic rabbits, the combination of heparin and sildenafil has an additive effect on the prolongation of 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 (regardless of whether the latter are taken 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 at the same time may cause symptoms of hypotension in some patients. When sildenafil needs to be used in combination with alpha-blockers, patients should have reached 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 has potential risks 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 conditions 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 condition 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 medication time have been reported in all post-marketing applications of PDE5 inhibitors.An observational case-crossover study evaluated the risk of developing NAION when using PDE5 inhibitors just before the onset of NAION (within 5 half-lives) compared to the use of PDE5 inhibitors in the previous period. 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 (such as optic disc "crowding") may be involved in the NAION that occurred in these studies. Rare postmarketing reports and the association between PDE5 inhibitor use and NAION in observational studies have not confirmed a causal relationship between PDE5 inhibitor use and NAION (see [Adverse Reactions]/Postmarketing Experience section).Published literature shows 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, doctors should consider whether they will be adversely affected by the use of PDE5 inhibitors. Individuals who have already experienced NAION have an increased risk of NAION recurrence. Doctors should inform patients who have experienced unilateral NAION that their risk of recurrence of NAION will increase 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. The risk of NAION in patients with "crowded" optic discs is also considered to be higher than that of the general population, but there is insufficient evidence to support the screening of potential users of PDE5 inhibitors (including this product) based on this rare disease. 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 whether 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 their risk of recurring NAION is increased regardless of whether vasodilator drugs such as PDE5 inhibitors may have adverse effects on them (see the "[Adverse Reactions]/Post-Marketing Experience/Special Sensations" section). Hearing loss: Physicians 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, which have been 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 the [Adverse Reactions]/Pre-Marketing Experience section and the Post-Marketing Experience section).Doctors should warn patients: After the approval of sildenafil citrate tablets for marketing 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 advice on sexually transmitted diseases: Sildenafil has no protective effect against sexually transmitted diseases. Patients should be informed of measures to prevent sexually transmitted diseases (including human immunodeficiency virus, HIV) as appropriate. Effects on the ability to drive and use machines Because dizziness and visual changes have been reported in clinical studies of sildenafil, patients should understand their possible reactions to sildenafil before driving and operating machines. The effects of sildenafil on the ability to drive and use machines have not been studied.
