Vardenafil Hydrochloride

Prescription

Торговые наименования: Vardenafil Hydrochloride

Лекарственная Форма

Tablet

Путь Введения

ORAL

Производитель

Bryant Ranch Prepack

About This Medication

11 DESCRIPTION Vardenafil hydrochloride tablets (vardenafil hydrochloride) are administered orally for the treatment of erectile dysfunction. This monohydrochloride salt of vardenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Vardenafil HCl is designated chemically as piperazine, 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1- f ][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-4-ethyl-, monohydrochloride and has the following structural formula: Vardenafil HCl is a nearly colorless, solid substance with a molecular weight of 579.1 g/mol and a solubility of 0.11 mg/mL in water. Vardenafil hydrochloride tablets are formulated as orange, round, tablets embossed with "2.5", "5", "10" or "20" on one side corresponding to 2.5 mg, 5 mg, 10 mg, and 20 mg of vardenafil, respectively. In addition to the active ingredient, vardenafil HCl, each tablet contains microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate, aspartame, titanium dioxide, ferric oxide red, and ferric oxide yellow.

Действующие Вещества

Компонент	Дозировка
Vardenafil Hydrochloride	-

Показания и Применение

1 INDICATIONS AND USAGE Vardenafil hydrochloride tablets are indicated for the treatment of erectile dysfunction. Vardenafil hydrochloride tablets are a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction. ( 1 )

Как это работает

12.1 Mechanism of Action Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMP-specific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has no effect in the absence of sexual stimulation. In vitro studies have shown that vardenafil is a selective inhibitor of PDE5. The inhibitory effect of vardenafil is more selective on PDE5 than for other known phosphodiesterases (>15-fold relative to PDE6, >130-fold relative to PDE1, >300-fold relative to PDE11, and >1,000-fold relative to PDE2, 3, 4, 7, 8, 9, and 10).

Дозировка и Способ Применения

2 DOSAGE AND ADMINISTRATION Vardenafil hydrochloride tablets are taken as needed: For most patients, the starting dose is 10 mg, up to once daily. Increase to 20 mg or decrease to 5 mg based on efficacy/tolerability. ( 2.1 ) A starting dose of 5 mg vardenafil hydrochloride tablets should be considered in patients ≥ 65 years of age. ( 2.3 ) Vardenafil hydrochloride tablets are taken orally, approximately 60 minutes before sexual activity. ( 2.1 ) The maximum recommended dosing frequency is one tablet per day. ( 2.1 ) Vardenafil hydrochloride tablets may be taken with or without food. ( 2.2 ) If taking strong or moderate inhibitors of CYP3A4, the dose of vardenafil hydrochloride tablets should be adjusted as follows ( 2.4 , 5.2 , 7.2 ): Ritonavir: No more than 2.5 mg in a 72-hour period Cobicistat: No more than 2.5 mg in a 72-hour period Indinavir, saquinavir, atazanavir, ketoconazole 400 mg daily, itraconazole 400 mg daily, clarithromycin: No more than 2.5 mg in a 24-hour period Ketoconazole 200 mg daily, itraconazole 200 mg daily, erythromycin: No more than 5 mg in a 24-hour period. In patients on stable alpha-blocker therapy the recommended starting dose of vardenafil hydrochloride tablets is 5 mg ( 2.4 , 5.6 ) The recommended starting dose of vardenafil hydrochloride tablets is 5 mg in patients with moderate hepatic impairment (Child-Pugh B). The maximum dose in patients with moderate hepatic impairment should not exceed 10 mg. ( 2.3 , 8.6 ) 2.1 General Dose Information For most patients, the recommended starting dose of vardenafil hydrochloride tablets is 10 mg, taken orally, as needed, approximately 60 minutes before sexual activity. The dose may be increased to a maximum recommended dose of 20 mg or decreased to 5 mg based on efficacy and side effects. The maximum recommended dosing frequency is once per day. Sexual stimulation is required for a response to treatment. 2.2 Use with Food Vardenafil hydrochloride tablets can be taken with or without food. 2.3 Use in Specific Populations Geriatrics: A starting dose of 5 mg vardenafil hydrochloride tablets should be considered in patients ≥65 years of age [see Use in Specific Populations (8.5) ]. Hepatic Impairment: For patients with moderate hepatic impairment (Child-Pugh B), a starting dose of 5 mg vardenafil hydrochloride tablets is recommended. The maximum dose in patients with moderate hepatic impairment should not exceed 10 mg. Do not use vardenafil hydrochloride tablets in patients with severe hepatic impairment (Child-Pugh C) [ see Warnings and Precautions (5.8) , Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Renal Impairment: Do not use vardenafil hydrochloride tablets in patients on renal dialysis [see Warnings and Precautions (5.9 ), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. 2.4 Concomitant Medications Nitrates: Concomitant use with nitrates and nitric oxide donors in any form is contraindicated [see Contraindications (4.1) ] Guanylate Cyclase (GC) Stimulators, such as riociguat : Concomitant use is contraindicated [see Contraindications (4.2) ]. CYP3A4 Inhibitors: The dosage of vardenafil hydrochloride tablets may require adjustment in patients receiving potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, atazanavir, cobicistat, and clarithromycin as well as in other patients receiving moderate CYP3A4 inhibitors such as erythromycin [see Drug Interactions (7.2 ) ]. If taking strong or moderate inhibitors of CYP3A4, the dose of vardenafil hydrochloride tablets should be adjusted as follows: Ritonavir: No more than 2.5 mg in a 72-hour period. Indinavir, saquinavir, atazanavir, ketoconazole 400 mg daily, itraconazole 400 mg daily, clarithromycin: No more than 2.5 mg in a 24-hour period. Ketoconazole 200 mg daily, itraconazole 200 mg daily, erythromycin: No more than 5 mg in a 24-hour period. Cobicistat: No more than 2.5 mg in a 72 hour period. Alpha-Blockers: In those patients who are stable on alpha-blocker therapy, phosphodiesterase type 5 (PDE5) inhibitors should be initiated at the lowest recommended starting dose. Concomitant treatment should be initiated only if the patient is stable on his alpha-blocker therapy. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure in patients taking a phosphodiesterase (PDE5) inhibitor including vardenafil. In those patients who are stable on alpha-blocker therapy, vardenafil hydrochloride tablets should be initiated at a dose of 5 mg (2.5 mg when used concomitantly with certain CYP3A4 inhibitors). [See Warnings and Precautions (5.6) and Drug Interactions (7.1) .] A time interval between dosing should be considered when vardenafil hydrochloride tablets are prescribed concomitantly with alpha-blocker therapy [see Clinical Pharmacology (12.2) ] .

Side Effects Overview

6 ADVERSE REACTIONS The following serious adverse reactions with the use of vardenafil hydrochloride tablets (vardenafil) are discussed elsewhere in the labeling: Cardiovascular Effects [see Contraindications (4.1) and Warnings and Precautions (5.1) ] Priapism [see Warnings and Precautions (5.3) ] Effects on Eye [see Warnings and Precautions (5.4) ] Sudden Hearing Loss [see Warnings and Precautions (5.5) ] QT Prolongation [see Warnings and Precautions (5.7) ] Most common adverse reactions reported ( ≥ 2% of patients) are headache, flushing, nasal congestion, dyspepsia, sinusitis, flu syndrome, dizziness, increased creatine kinase, nausea, back pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Vardenafil hydrochloride tablets were administered to over 4430 men (mean age 56, range 18-89 years; 81% White, 6% Black, 2% Asian, 2% Hispanic and 9% Other) during controlled and uncontrolled clinical trials worldwide. Over 2200 patients were treated for 6 months or longer and 880 patients were treated for at least 1 year. In placebo-controlled clinical trials, the discontinuation rate due to adverse events was 3.4% for vardenafil hydrochloride tablets compared to 1.1% for placebo. When vardenafil hydrochloride tablets were taken as recommended in placebo-controlled clinical trials, the following adverse reactions were reported (see Table 1 ). Table 1: Adverse Reactions Reported By ≥2% of Patients Treated with Vardenafil Hydrochloride Tablets and More Frequent on Drug than Placebo in Fixed and Flexible Flexible dose studies started all patients at vardenafil hydrochloride tablets 10 mg and allowed decrease in dose to 5 mg or increase in dose to 20 mg based on side effects and efficacy. Dose Randomized, Controlled Trials of 5 mg, 10 mg, or 20 mg Vardenafil Adverse Reaction Percentage of Patients Reporting Reactions Placebo N = 1199 Vardenafil Hydrochloride Tablets N = 2203 Headache 4% 15% Flushing 1% 11% Rhinitis 3% 9% Dyspepsia 1% 4% Accidental Injury All the events listed in the above table were deemed to be adverse drug reactions with the exception of accidental injury. 2% 3% Sinusitis 1% 3% Flu Syndrome 2% 3% Dizziness 1% 2% Increased Creatine Kinase 1% 2% Nausea 1% 2% Back pain was reported in 2.0% of patients treated with vardenafil hydrochloride tablets and 1.7% of patients on placebo. Placebo-controlled trials suggested a dose effect in the incidence of some adverse reactions (headache, flushing, dyspepsia, nausea, and rhinitis) over the 5 mg, 10 mg, and 20 mg doses of vardenafil hydrochloride tablets. All Vardenafil Studies: Vardenafil hydrochloride tablets and vardenafil orally disintegrating tablets have been administered to over 17,000 men (mean age 54.5, range 18–89 years; 70% White, 5% Black, 13% Asian, 4% Hispanic and 8% Other) during controlled and uncontrolled clinical trials worldwide. The number of patients treated for 6 months or longer was 3357, and 1350 patients were treated for at least 1 year. In the placebo-controlled clinical trials for vardenafil hydrochloride tablets and vardenafil orally disintegrating tablets, the discontinuation rate due to adverse events was 1.9% for vardenafil compared to 0.8% for placebo. The following section identifies additional, less frequent adverse reactions (<2%) reported during the clinical development of vardenafil hydrochloride tablets and vardenafil orally disintegrating tablets. Excluded from this list are those adverse reactions that are infrequent and minor, those events that may be commonly observed in the absence of drug therapy, and those events that are not reasonably associated with the drug: Body as a whole: allergic edema and angioedema, feeling unwell, allergic reactions, chest pain Auditory: tinnitus, vertigo Cardiovascular: palpitation, tachycardia, angina pectoris, myocardial infarction, ventricular tachyarrhythmias, hypotension Digestive: nausea, gastrointestinal and abdominal pain, dry mouth, diarrhea, gastroesophageal reflux disease, gastritis, vomiting, increase in transaminases Musculoskeletal: increase in creatine phosphokinase (CPK), increased muscle tone and cramping, myalgia Nervous: paresthesia and dysesthesia, somnolence, sleep disorder, syncope, amnesia, seizure Respiratory: dyspnea, sinus congestion Skin and appendages: erythema, rash Ophthalmologic: visual disturbance, ocular hyperemia, visual color distortions, eye pain and eye discomfort, photophobia, increase in intraocular pressure, conjunctivitis Urogenital: increase in erection, priapism 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of vardenafil hydrochloride tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure. Ophthalmologic: Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio ("crowded disc"), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking [see Warnings and Precautions (5.4) and Patient Counseling Information (17) ] . Visual disturbances including vision loss (temporary or permanent), such as visual field defect, retinal vein occlusion, and reduced visual acuity, have also been reported rarely in postmarketing experience. It is not possible to determine whether these events are related directly to the use of vardenafil. Neurologic: Seizure, seizure recurrence and transient global amnesia have been reported postmarketing in temporal association with vardenafil. Otologic: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. In some cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of vardenafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Patient Counseling Information (17) ] .

Предупреждения и Меры Предосторожности

5 WARNINGS AND PRECAUTIONS The evaluation of erectile dysfunction should include a medical assessment, a determination of potential underlying causes and the identification of appropriate treatment. Before prescribing vardenafil hydrochloride tablets, it is important to note the following: Cardiovascular Effects : Patients should not use vardenafil hydrochloride tablets if sex is inadvisable due to cardiovascular status. ( 5.1 ) Risk of Priapism : In the event that an erection lasts more than 4 hours, the patient should seek immediate medical assistance. ( 5.3 ) Effects on the Eye: Patients should stop use of vardenafil hydrochloride tablets, and seek medical attention in the event of sudden loss of vision in one or both eyes, which could be a sign of nonarteritic anterior ischemic optic neuropathy (NAION). Vardenafil hydrochloride tablets should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION. Patients with a "crowded" optic disc may also be at an increased risk of NAION. ( 5.4 , 6.2 ) Sudden Hearing Loss : Patients should stop vardenafil hydrochloride tablets and seek medical attention in the event of sudden decrease or loss in hearing. ( 5.5 , 6.2 ) Alpha-Blockers : Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. In some patients, concomitant use of these two drug classes can lower blood pressure significantly leading to symptomatic hypotension (for example, fainting). ( 2.4 , 5.6 ) QT Prolongation : Patients with congenital QT syndrome or taking class IA or III antiarrhythmics should avoid using vardenafil hydrochloride tablets. ( 5.7 , 12.2 ) Phenylketonurics : Contains Phenylalanine ( 5.13 ) 5.1 Cardiovascular Effects General Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Therefore, treatment for erectile dysfunction, including vardenafil hydrochloride tablets, should not be used in men for whom sexual activity is not recommended because of their underlying cardiovascular status. There are no controlled clinical data on the safety or efficacy of vardenafil in the following patients; and therefore its use is not recommended until further information is available: unstable angina; hypotension (resting systolic blood pressure of <90 mmHg); uncontrolled hypertension (>170/110 mmHg); recent history of stroke, life-threatening arrhythmia, or myocardial infarction (within the last 6 months); severe cardiac failure. Left Ventricular Outflow Obstruction Patients with left ventricular outflow obstruction, (for example, aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators including PDE5 inhibitors. Blood Pressure Effects Vardenafil hydrochloride tablets have systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 7 mmHg systolic and 8 mmHg diastolic) [see Clinical Pharmacology (12.2) ] . While this normally would be expected to be of little consequence in most patients, prior to prescribing vardenafil hydrochloride tablets, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. 5.2 Potential for Drug Interactions with Strong or Moderate CYP3A4 Inhibitors Concomitant administration with strong CYP3A4 inhibitors (such as ritonavir, indinavir, cobicistat, ketoconazole) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. Dosage adjustment is necessary when vardenafil hydrochloride tablets are administered with certain CYP3A4 inhibitors [see Dosage and Administration (2.4) , and Drug Interactions (7.2) ]. Long-term safety information is not available on the concomitant administration of vardenafil with HIV protease inhibitors. 5.3 Risk of Priapism There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds, including vardenafil. In the event that an erection persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result. Vardenafil hydrochloride tablets should be used with caution by patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease) or by patients who have conditions that may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia). 5.4 Effects on the Eye Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including vardenafil hydrochloride tablets, and seek medical attention in the event of sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5–11.8 cases per 100,000 in males aged ≥50. An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. Neither the rare postmarketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [see Adverse Reactions (6.2) ] . Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, PDE5 inhibitors, including vardenafil hydrochloride tablets, should be used with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with "crowded" optic disc are also considered at greater risk for NAION compared to the general population, however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including vardenafil hydrochloride tablets, for this uncommon condition. Vardenafil hydrochloride tablets have not been evaluated in patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, therefore its use is not recommended until further information is available in those patients. 5.5 Sudden Hearing Loss Physicians should advise patients to stop taking all PDE5 inhibitors, including vardenafil hydrochloride tablets, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including vardenafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6.2) ]. 5.6 Alpha-Blockers Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including vardenafil hydrochloride tablets, 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 (for example, fainting) [see Drug Interactions (7.1) and Clinical Pharmacology (12.2) ] . 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 recommended starting dose [see Dosage and Administration (2.4) ] . In those patients already taking an optimized dose of 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 in patients 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. 5.7 Congenital or Acquired QT Prolongation In a study of the effect of vardenafil hydrochloride tablets on QT interval in 59 healthy males [see Clinical Pharmacology (12.2) ] , therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil and the active control moxifloxacin (400 mg) produced similar increases in QTc interval. A postmarketing study evaluating the effect of combining vardenafil hydrochloride tablets with another drug of comparable QT effect showed an additive QT effect when compared with either drug alone [see Clinical Pharmacology (12.2) ] . These observations should be considered in clinical decisions when prescribing vardenafil hydrochloride tablets to patients with known history of QT prolongation or patients who are taking medications known to prolong the QT interval. Patients taking Class 1A (for example. quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic medications or those with congenital QT prolongation, should avoid using vardenafil hydrochloride tablets. 5.8 Hepatic Impairment Dosage adjustment is necessary in patients with moderate hepatic impairment (Child-Pugh B). Do not use vardenafil hydrochloride tablets in patients with severe (Child-Pugh C) hepatic impairment. [See Dosage and Administration (2.3) Clinical Pharmacology (12.3) and Use in Specific Populations (8.6) ]. 5.9 Renal Impairment Do not use vardenafil hydrochloride tablets in patients on renal dialysis, as vardenafil has not been evaluated in this population [see Dosage and Administration (2.3) and Use in Specific Populations (8.7) ]. 5.10 Combination with Other Erectile Dysfunction Therapies The safety and efficacy of vardenafil hydrochloride tablets used in combination with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. 5.11 Effects on Bleeding In humans, vardenafil alone in doses up to 20 mg does not prolong the bleeding time. There is no clinical evidence of any additive prolongation of the bleeding time when vardenafil is administered with aspirin. Vardenafil hydrochloride tablets have not been administered to patients with bleeding disorders or significant active peptic ulceration. Therefore vardenafil hydrochloride tablets should be administered to these patients after careful benefit-risk assessment. 5.12 Sexually Transmitted Disease The use of vardenafil hydrochloride tablets offers no protection against sexually transmitted diseases. Counseling of patients about protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), should be considered. 5.13 Risks in Patients with Phenylketonuria Phenylalanine can be harmful to patients with phenylketonuria (PKU). Vardenafil hydrochloride tablets contain phenylalanine, a component of aspartame. Each 2.5 mg vardenafil hydrochloride tablet contains 0.7 mg phenylalanine; each 5 mg tablet contains 1.4 mg phenylalanine; each 10 mg tablet contains 2.8 mg phenylalanine; each 20 mg tablet contains 5.6 mg phenylalanine. Before prescribing vardenafil hydrochloride tablets in a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including vardenafil hydrochloride tablets.

Противопоказания

4 CONTRAINDICATIONS Administration with nitrates and nitric oxide donors ( 2.4 , 4.1 ) Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 2.4 , 4.2 ) 4.1 Nitrates Administration of vardenafil hydrochloride tablets with nitrates (either regularly and/or intermittently) and nitric oxide donors is contraindicated [see Clinical Pharmacology (12.2) ] . Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors, including vardenafil hydrochloride tablets, may potentiate the hypotensive effects of nitrates. A suitable time interval following dosing of vardenafil hydrochloride tablets for the safe administration of nitrates or nitric oxide donors has not been determined. 4.2 Guanylate Cyclase (GC) Stimulators Do not use vardenafil hydrochloride tablets in patients who are using a GC stimulator, such as riociguat. PDE5 inhibitors, including vardenafil hydrochloride tablets may potentiate the hypotensive effects of GC stimulators.

Фармакокинетика

12.3 Pharmacokinetics The pharmacokinetics of vardenafil are approximately dose proportional over the recommended dose range. Absorption Mean vardenafil plasma concentrations measured after the administration of a single oral dose of 20 mg to healthy male volunteers are depicted in Figure 8. Figure 8: Plasma Vardenafil Concentration (Mean ± SD) Curve for a Single 20 mg Vardenafil Hydrochloride Tablets Dose Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%. Maximum observed plasma concentrations after a single 20 mg dose in healthy volunteers are usually reached between 30 minutes and 2 hours (median 60 minutes) after oral dosing in the fasted state. Two food-effect studies were conducted which showed that high- fat meals caused a reduction in C max by 18%-50%. Distribution The mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution. Vardenafil and its major circulating metabolite, M1, are highly bound to plasma proteins (about 95% for parent drug and M1). This protein binding is reversible and independent of total drug concentrations. Following a single oral dose of 20 mg vardenafil in healthy volunteers, a mean of 0.00018% of the administered dose was obtained in semen 1.5 hours after dosing. Metabolism Vardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major circulating metabolite, M1, results from desethylation at the piperazine moiety of vardenafil. M1 is subject to further metabolism. The plasma concentration of M1 is approximately 26% that of the parent compound. This metabolite shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for PDE5 28% of that of vardenafil. Therefore, M1 accounts for approximately 7% of total pharmacologic activity. Excretion The total body clearance of vardenafil is 56 L/h, and the terminal half-life of vardenafil and its primary metabolite (M1) is approximately 4-5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose). Pharmacokinetics in Specific Populations Pediatrics Vardenafil hydrochloride tablets are not indicated for use in pediatric patients. Vardenafil trials were not conducted in the pediatric population. Geriatric In a healthy volunteer study of elderly males (≥65 years) and younger males (18–45 years), mean C max and AUC were 34% and 52% higher, respectively, in the elderly males [see Use in Specific Populations (8.5) ]. Hepatic Impairment In volunteers with mild hepatic impairment (Child-Pugh A), the C max and AUC following a 10 mg vardenafil dose were increased by 22% and 17%, respectively, compared to healthy control subjects. In volunteers with moderate hepatic impairment (Child-Pugh B), the C max and AUC following a 10 mg vardenafil dose were increased by 130% and 160%, respectively, compared to healthy control subjects. Vardenafil has not been evaluated in patients with severe (Child-Pugh C) hepatic impairment. [See Dosage and Administration (2.3) , Warnings and Precautions (5.8) , and Use in Specific Populations (8.6) .] Renal Impairment In male volunteers with CLcr = 50–80 mL/min, the pharmacokinetics of vardenafil were similar to those observed in a control group with CLcr >80 mL/min. In male volunteers with CLcr = 30–50 mL/min or CLcr <30 mL/min renal impairment groups, the AUC of vardenafil was 20–30% higher compared to that observed in a control group with CLcr >80 mL/min). Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis. [See Dosage and Administration (2.3) , Warnings and Precautions (5.9) , and Use in Specific Populations (8.7) .]

Frequently Asked Questions

1 INDICATIONS AND USAGE Vardenafil hydrochloride tablets are indicated for the treatment of erectile dysfunction. Vardenafil hydrochloride tablets are a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction. ( 1 )

2 DOSAGE AND ADMINISTRATION Vardenafil hydrochloride tablets are taken as needed: For most patients, the starting dose is 10 mg, up to once daily. Increase to 20 mg or decrease to 5 mg based on efficacy/tolerability. ( 2.1 ) A starting dose of 5 mg vardenafil hydrochloride tablets should be considered in patients ≥ 65 years of age. ( 2.3 ) Vardenafil hydrochloride tablets are taken orally, approximately 60 minutes before sexual activity. ( 2.1 ) The maximum recommended dosing …

5 WARNINGS AND PRECAUTIONS The evaluation of erectile dysfunction should include a medical assessment, a determination of potential underlying causes and the identification of appropriate treatment. Before prescribing vardenafil hydrochloride tablets, it is important to note the following: Cardiovascular Effects : Patients should not use vardenafil hydrochloride tablets if sex is inadvisable due to cardiovascular status. ( 5.1 ) Risk of Priapism : In the event that an erection lasts more than 4 hours, the patient should seek immediate medical …

4 CONTRAINDICATIONS Administration with nitrates and nitric oxide donors ( 2.4 , 4.1 ) Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 2.4 , 4.2 ) 4.1 Nitrates Administration of vardenafil hydrochloride tablets with nitrates (either regularly and/or intermittently) and nitric oxide donors is contraindicated [see Clinical Pharmacology (12.2) ] . Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors, including vardenafil hydrochloride tablets, may potentiate the hypotensive effects of nitrates. …

Vardenafil Hydrochloride is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

Similar Tablet Products

Sulfamethoxazole And Trimethoprim

Perphenazine

Sitagliptin

Echinacea Purpurea

Silicium Metallicum

Rabeprazole Sodium

Browse all Tablet products →

References & Data Sources

• DailyMed — Vardenafil Hydrochloride drug label (National Library of Medicine)
• openFDA — Vardenafil Hydrochloride label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 349480 (NLM Normalized Drug Names)
• NDC Directory — Vardenafil Hydrochloride (FDA National Drug Code)

Медицинский Отказ от Ответственности

Информация на данной странице предназначена исключительно в образовательных целях и не должна использоваться в качестве замены профессиональной медицинской консультации, диагностики или лечения.

Всегда обращайтесь за советом к своему врачу или иному квалифицированному медицинскому работнику по любым вопросам, связанным с состоянием здоровья или лекарственными препаратами.

Источники данных: DailyMed (NLM), openFDA, MFDS