Vardenafil hydrochloride tablets are indicated for the treatment of male erectile dysfunction
The main ingredient of this product is vardenafil hydrochloride.
Its chemical name is: 2-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulfa)-phenyl]-5-methyl-7-propyl-3H-imidazole [5 ,1-f]-[1,2,4]Triazin-4-one monohydrochloride
Its structural formula is:
Molecular formula: C23H32N6O4S·HCl·3H2O
Molecular weight: 579.1
This product is a light orange to dark orange film-coated tablet, which appears white after removing the film coating.
Treatment of erectile dysfunction in men.
5mg, 10mg, 20mg
The recommended starting dose is 10 mg, taken approximately 25-60 minutes before sexual intercourse. In clinical trials, taking 4-5 hours before sexual intercourse, the drug still shows efficacy. The maximum recommended dosage frequency is once a day. Vardenafil can be taken with food or alone. Sexual stimulation is required as an instinctive response for treatment.
"According to the efficacy and tolerability, the dose can be increased to 20mg or decreased to 5mg. The maximum recommended dose is 20 mg per day.
Patients with mild liver damage (Child-Pugh A) do not need to adjust the dose; patients with moderate liver damage (Child-Pugh B), due to the reduced clearance of vardenafil, the recommended starting dose is 5 mg, and then based on tolerability And the drug effect gradually increased to 10mg; the pharmacokinetic study of vardenafil in patients with severe liver damage (Child-Pugh C) has not been carried out.
Patients with mild, moderate or severe renal impairment do not need to adjust the dose. The pharmacokinetic study of vardenafil in dialysis patients has not been carried out.
Some patients taking vardenafil and alpha-blockers at the same time may cause symptomatic hypotension. Only when patients receive α-receptor blockers in stable condition, can they be combined with drugs. For patients who are receiving α-blockers for stable disease, the dose of vardenafil should be the lowest recommended starting dose of 5 mg, and tamsulosin can be taken at any time. When vardenafil is used in combination with other alpha-blockers, there should be a certain interval of medication. For patients who have taken the optimal dose of vardenafil, the application of alpha-blockers should start from the lowest dose. For patients taking PDF5 inhibitors (including vardenafil), an increase in the dose of alpha-blockers may cause the patient's blood pressure to drop further.
"Patients taking certain CYP3A4 inhibitors may need to adjust the dose of vardenafil (such as ketoconazole, itraconazole, ritonavir, indinavir, and erythromycin).
When erythromycin is used at the same time, the maximum dose of vardenafil does not exceed 5 mg. When taking ketoconazole and itraconazole, the maximum dose of vardenafil should not exceed 5 mg. When the dose of ketoconazole or itraconazole exceeds 200 mg, vardenafil cannot be taken. Avoid taking the powerful CYP3A4 inhibitors indinavir and ritonavir at the same time.
In global clinical trials (as of March 2004), more than 9,500 patients took vardenafil and it was well tolerated. Adverse events that occur are usually transient and mild to moderate.
placebo controlled clinical trials:
When vardenafil was taken at the recommended dose, the following adverse reactions were reported in placebo-controlled clinical trials (as of March 2004):
Global clinical trials:
Global clinical trials have reported that patients have the following adverse reactions after taking vardenafil (as of March 2004). Including the key terms designated by the WHO (Critical terms: may be related to serious diseases and should attract special attention) or other clinically related adverse reactions:
When taking vardenafil for sexual activity, the occurrence of myocardial infarction (MI) has been reported, but it cannot be determined that myocardial infarction is related to vardenafil, or related to sexual activity, or the patient’s underlying cardiovascular disease, or a combination of these factors The role is directly related.
After the listing of PDE5 inhibitors (including Levitra), there have been reports of a very small number of patients with non-arteritic anterior ischemic optic neuropathy (NAION). NAION is a disease that can cause vision loss and even permanent blindness. Most, but not all, of these patients have anatomical or vascular risk factors that are prone to NAION, including: small cup-to-disc ratio (small optic papilla), age over 50, diabetes, hypertension, coronary heart disease, and hyperlipidemia , Smoking. Whether the above-mentioned events are directly related to the use of PDE5 inhibitors or the patient's potential vascular risk factors or anatomical defects, or the combined effect of these factors, or other factors is still unclear.
After PDE5 inhibitors were marketed (including Levitra), it has been reported that a very small number of patients have visual impairment, including blindness (temporary or permanent). Whether these events are directly related to the use of PDE5 inhibitors, the patient's potential vascular risk factors or anatomical defects, or a combination of these factors, or other factors is still unclear.
After the listing of PDE5 inhibitors (including Levitra) and in clinical trials, it has been reported that a small number of patients can cause sudden deafness or hearing loss. Whether these events are directly related to the use of Levitra, the patient's potential risk factors for hearing loss, or the combined effects of these factors, or other factors is still unclear.
1. It is forbidden for patients who have allergic symptoms to any component of the drug (active or inactive).
2. Same as PDE inhibition in the NO/cGMP pathway, PDE5 inhibitors may enhance the antihypertensive effect of nitrate drugs. Therefore, patients taking nitrates or nitric oxide donors should avoid concurrent use of vardenafil.
3. Avoid the simultaneous use of HIV protein kinase inhibitor indinavir or ritonavir and vardenafil, because they are potent CYP3A4 inhibitors.
Because sexual activity is accompanied by a certain degree of heart risk, doctors should first consider their heart conditions before taking any treatment for erectile dysfunction. The vasodilator properties of vardenafil may cause a temporary slight decrease in blood pressure. Patients with left ventricular outflow disorders, such as aortic stenosis and idiopathic hypertrophic aortic subvalvular stenosis, may be sensitive to vasodilator drugs, including PDE5 inhibitors. Due to the potential risk of the heart, it is not recommended for patients with heart disease to have sexual intercourse. Therefore, drugs for the treatment of erectile dysfunction are usually not used.
A study of 59 healthy male subjects taking vardenafil on the QT interval showed that therapeutic doses (10 mg) and overdose (80 mg) of vardenafil lead to prolongation of QTc intervals. A post-marketing study showed that when vardenafil is used in combination with another drug that affects the QT interval, it has a cumulative effect on the QT interval compared with each drug alone. Therefore, for patients with a history of QT interval prolonging or taking drugs that prolong the QT interval, this point must be taken into consideration when clinically using vardenafil. Patients with congenital prolonged QT interval (long QT syndrome) and taking class IA (such as quinidine, procainamide) or class III (such as amiodarone, sotalol) antiarrhythmic drugs should be avoided Take vardenafil.
For patients with anatomical malformations of the penis (such as angulation, cavernous fibrosis, Peyronie's disease), or penile erections that cannot be resolved (such as sickle cell disease, multiple myeloma, and leukemia), treatment of erectile dysfunction is necessary Use medication with caution.
When combined with other treatments for erectile dysfunction, the safety and efficacy of vardenafil have not been studied, so the combined use is not recommended.
For patients with the following conditions, the safety of vardenafil has not been studied, and vardenafil is recommended unless there is further information: severe liver disease, end-stage renal disease requiring dialysis, hypotension (resting systolic blood pressure [90 mmHg), Recently suffered from stroke or myocardial infarction (within 6 months), unstable angina, family degenerative eye diseases such as retinitis pigmentosa.
It has been reported that transient blindness and non-arteritic anterior ischemic optic neuropathy are related to taking Levitra and other PDE5 inhibitors. Patients should be advised to stop taking Levitra in the event of sudden blindness and seek medical treatment immediately.
Vardenafil has not been used in patients with bleeding disorders or active peptic ulcers, so it should only be used after careful benefit-risk assessment.
Vardenafil has no effect on bleeding time when used alone or in combination with aspirin.
Human platelet in vitro tests show that vardenafil alone does not inhibit platelet aggregation induced by multiple platelet factors. During overdose treatment, vardenafil was observed to slightly enhance the anticoagulant effects of sodium nitroprusside and nitric oxide donors in a concentration-dependent manner. Vardenafil combined with heparin has no effect on the bleeding time of rats, but its interaction has not been studied in humans.
The ability to drive and operate machinery and equipment:
Patients should consider their reactions to vardenafil before driving and operating machinery.
Medication for pregnant and lactating women
Children (birth to 16 years): Vardenafil is not suitable for children.
In elderly patients (≥65 years), the clearance rate of vardenafil is reduced, and the starting dose is considered to be 5 mg.
Vardenafil is mainly metabolized by cytochrome P450 (CYP) isoenzyme 3A4 through liver enzymes. CYP3A5 and CYP2C isoenzymes play a certain role in its metabolism. Therefore, inhibitors of these enzymes can reduce the clearance of vardenafil.
Cimetidine: In healthy volunteers, the combined use of vardenafil (20 mg) and non-specific cytochrome P450 inhibitor cimetidine (400 mg, twice a day) does not affect the AUC of vardenafil And Cmax.
Erythromycin: In healthy volunteers, the combined use of vardenafil (5mg) and CYP3A4 inhibitor erythromycin (500 mg, three times a day) can increase the AUC and Cmax of vardenafil by 300% and 200, respectively %.
Ketoconazole: In healthy volunteers, the combined use of vardenafil (5 mg) and strong CYP3A4 inhibitor ketoconazole (200 mg) can increase the AUC and Cmax of vardenafil by 900% and 300%, respectively.
Indinavir: The combined use of vardenafil (10 mg) and HIV protease inhibitor indinavir (800 mg, three times a day) resulted in a 1500% increase in AUC of vardenafil and a 600% increase in Cmax. After 24 hours of combination therapy, the plasma concentration of vardenafil is approximately 4% of its maximum plasma concentration (Cmax).
Ritonavir: (600 mg, twice a day) and vardenafil 5mg are used at the same time, resulting in a 13-fold increase in the Cmax of vardenafil and a 49-fold increase in AUC0-24. The strong CYP3A4 inhibitor ritonavir (which also inhibits the CYP2C9 enzyme) can block the transhepatic metabolism of vardenafil, and ritonavir significantly prolongs the half-life of vardenafil to 25.7 hours.
Simultaneous use of P450 (CYP) 3A4 inhibitors ketoconazole, itraconazole, indinavir and ritonavir can significantly increase vardenafil plasma levels. When using erythromycin at the same time, the maximum dose of vardenafil does not exceed 5 mg.
When taking ketoconazole or itraconazole, the maximum dose of vardenafil should not exceed 5 mg. When the dose of ketoconazole or itraconazole exceeds 200 mg, vardenafil should not be taken. Avoid taking the powerful CYP3A4 inhibitors indinavir and ritonavir at the same time.
Nitrates, nitric oxide donors:
A study of 18 healthy subjects showed that when nitroglycerin (0.4mg) was sublingually taken within a certain period of time (24 hours to 1 hour), vardenafil (10mg) was not found to be strong The blood pressure lowering effect.
After taking vardenafil for 1 to 4 hours in healthy middle-aged subjects, sublingual administration of nitroglycerin (0.4mg) increased blood pressure. This effect was not observed when using Vardenafil 20 mg 24 hours before taking nitroglycerin.
There is currently no data to prove that the combined use of vardenafil and nitrate drugs in patients has the potential to lower blood pressure, and the combined use of drugs should be avoided.
When vardenafil (20 mg) is used in combination with glibenclamide (3.5 mg), it does not affect the relative bioavailability of glibenclamide (it does not affect the AUC and Cmax of glibenclamide). There is no data showing that the combined application of glibenclamide affects the pharmacokinetics of vardenafil.
When vardenafil (20 mg) is used in combination with warfarin (25 mg), no interaction between pharmacokinetics and pharmacodynamics (prothrombin time and clotting factors II, VII and X) has been found. The combined use of warfarin does not affect the pharmacokinetics of vardenafil.
When vardenafil (20 mg) was used in combination with nifedipine (30 or 60 mg), no related pharmacokinetic interactions were found, and no pharmacodynamic interactions were found (compared to placebo, Vardenafil caused an additional reduction in blood pressure, with an average reduction in systolic and diastolic blood pressure in the supine position by 5.9 mm Hg and 5.2 mm Hg, respectively).
Since α-blockers can significantly lower blood pressure, especially orthostatic hypotension and fainting, the interaction between α-blockers and vardenafil has been studied. Volunteers with normal blood pressure, short-term daily combined use of terazosin 10 mg or tamsulosin 0.4 mg and vardenafil 10 mg and 20 mg daily. Both drugs reach Cmax at the same time, which can cause orthostatic systolic blood pressure in some cases [85mmHg, or reduce 30mmHg with orthostatic hypotension. When Cmax is separated by 6 hours, the above situation occurs less frequently, especially when taking tamsulosin. When vardenafil and tamsulosin were used in combination, the orthostatic systolic blood pressure and diastolic blood pressure were reduced by an average of 8 mmHg and 7 mmHg, respectively (regardless of the length of the interval between medications). Further studies have been conducted on patients with benign prostatic hyperplasia (BPH) who have received long-term alpha-blocker therapy (tamsulosin 0.4mg or terazosin 5mg, 10mg) taking vardenafil 5mg, orthostatic systolic blood pressure and relaxation The blood pressure was reduced by 6 mmHg and 3 mmHg respectively (regardless of the length of the intermittent medication or the alpha-blocker). After the combined application of tamsulosin and vardenafil, three patients had at least one short-term orthostatic systolic blood pressure [85 mmHg, but no symptoms of hypotension; patients receiving terazosin also took vardenafil 5mg, In 5 cases, the orthostatic systolic blood pressure decreased by 30mmHg (2 cases in the placebo group), and 1 case had the orthostatic systolic blood pressure [85 mmHg with dizziness. However, the above phenomenon will not occur when taking vardenafil 5mg and terazosin 6 hours apart.
When tegoxin (0.375 mg) reaches a steady state, use vardenafil (20 mg) in combination once every other day for more than 14 days