Short Excursus to Levitra (Vardenafil)
Levitra is a pharmacological product for restoration of erectile dysfunction. It belongs to the group of PDE5 inhibitors. Levitra presentation form is tableted. Double radius tablets are covered with film coat with rather rough surface. Its color varies from grey-orange to light-orange. The one side of Levitra pill has engraving 5, 10 or 20, whereas the other one has a Bayer branded cross.
Levitra active substance is vardenafil hydrochloride trihydrate in the quantity of 5, 10 and 20mg. Auxiliary components are as follows: magnesium stearate, crospovidone, anhydrous colloidal silicon dioxide, microcrystalline cellulose. In the composition of film coat: hypromellose, macrogol 400, titania, iron oxide red, iron oxide yellow.
Indications to Administration
Levitra is indicative in all possible cases of erectile dysfunction, incapacity of a man to achieve and preserve erection required to fulfilling of sexual intercourse.
- Combination with indinavir, ritonavir and other inhibitors of HIV protease;
- Co-administration with nitrogen oxide donors or nitrates;
- Age under 16 years;
- Hypersensitivity to medications components;
- Medication is not to be used by women;
Patients should take Levitra carefully in the following cases:
- Anatomic deformation of penis (Peyronie’s disease, cavernosal fibrosis, angulation);
- Congenital QT interval elongation;
- Pathological conditions predisposing to priapism (erythroid myeloma, sickle-cell disease, leukemia);
- Pronounced impairment of hepatic function;
- Terminal degree of renal disorder;
- Arterial hypertension (systolic pressure at rest is less than 90 mm of mercury);
- Myocardial infarction or apoplectic attack in the recent medical history;
- Unstable angina;
- Degenerative hereditary disorders of eye retina (including pigmented retinitis);
- Aggravation of peptic ulcer;
- Underlying risk for bleeding;
- Idiopathic subaortic or/and aortic stenosis.
Posology and Administration
Tablets are taken perorally regardless of food acceptance. Adequate efficiency of the medication is achieved in case of sufficient level of sexual stimulation. Recommended dosage is 10mg once a day not longer than 5 hours before sexual activity, usually 0.5-1 hour before sexual intercourse. The dosage may be reduced to 25mg or exceeded, but not more than up to 20mg in accordance with individual tolerability and efficiency of medication.
Dosing schedule does not require correction in case of mild or insignificantly pronounced hepatic or renal impairments, and intake by elderly patients. Patients suffering from mild hepatic impairment should start taking the medication in dosage of 5mg per day. Afterwards the dose may be increased up to 10 and 20mg considering efficiency and tolerability of Levitra.
Possibility of side-effects occurrence: ≥10% – often, ≥1% – seldom, ≥0,1%-<1% – sometimes.
Cardio-vascular system: often – blushing (feeling of heat, sudden periodical blushing of face); sometimes – arterial blood pressure increase, postural hypotension, arterial blood pressure drop, myocardial ischemia, cardiac angina.
Nervous system: often – headache; seldom – vertigo; sometimes – anxiety, drowsiness, syncope.
Alimentary system: sometimes – nausea, dyspepsia, functional hepatic tests impairment (increase of glutamyl pyruvic transaminase, serum glutamate-oxaloacetate-transaminase, and gamma-glutamyl transpeptidase).
Reproductive system: sometimes – painful erection, prolongation of erection, priapism.
Respiratory system: sometimes – difficult breathing, congestive hyperemia of nasal mucosa (rhinitis, swollen mucosa, rhinorrhea), nasal bleeding, laryngeal edema.
Musculo-skeletal system: sometimes – backache, myodnia, creatine phosphokinase increase, muscular tone increase.
Visual organ: sometimes – impairment of visual brightness, increase of tearing of eyes, increase of ophthalmotonous pressure
Dermatological reactions: sometimes – facial edema, photosensitivity.
Other: sometimes – hypersensitivity reactions.
Besides, according to post-marketing research studies, cases of vision impairment are reported due to ischemic optic neuropathy up to steady vision loss. Very often the afore-mentioned conditions occur among patients with contributing risk factors, such as smoking, age above 50 years, anatomic defect of papilla nervi optici, diabetes, atherosclerotic cardiovascular disease, arterial hypertension, hyperlipidemia. The connection between development of ischemic optic neuropathy and Levitra intake is not stated yet.
Special Note and Dose Calculation
Levitra dose in case of cardio-vascular disorders
Levitra prescription must be made by a doctor after estimation of cardio-vascular system of a patient, since the risk of cardiac condition complications during sexual intercourse increases. Levitra is not to be prescribed to men with co-morbidity of cardio-vascular system for which sexual activity of counter-indicative. Application of vardenafil takes vasodilatory action as well and may cause insignificant or mild arterial blood pressure drop. The obstruction of outflow tract from aortic ventricle (including aortic stenosis, idiopathic hypertrophic subaortic stenosis) may cause hypersensitivity of a patient to the action of PDE5 inhibitor. Patients suffering from congenital QT interval elongation or during the period of quinidine, procaine hydrochloride, amiodarone, sotalol, and other antiarrhythmic drugs of 1A class and 3 class administration should not be prescribed to use Levitra, since even the dose of 10mg of the medication causes QT interval elongation. Due to the absence of Levitra therapy consequences, it is not to be taken in case of severe hepatic failure, terminal stage of renal disease (requiring hemodialysis conduction), arterial hypotension, myocardial infraction or apoplectic attack within the last 6 months, unstable angina, hereditary degenerative pathology of eye retina (pigmented retinitis). In case of a sudden vision loss, the medication intake must be stopped immediately, and a patient must seek immediate medical attendance.
Levitra dosage with alpha-adrenergic blocking agents
Combination with alpha-adrenergic blocking agents may lead to the development of arterial hypotension, since both medicines take vasodilatory action. This combination is admissible only in case of stable arterial blood pressure on the setting of alpha-adrenergic blocking agents taken along with Levitra in dosage of not more than 5mg. Vardenafil administration may coincide in time with tamsulosin intake, whereas other alpha-adrenergic blocking agents should not be co-administered with the medicine. In case Levitra is combined with alpha-adrenergic blocking agents, its intake should be started with minimal dose. Gradual increase of alpha-adrenergic blocking agents dose on the setting of PDE5 inhibitors therapy may cause further arterial blood pressure drop.
Posology with other drugs
- In case of simultaneous intake with itraconazole, ketoconazole, or erythromycin, vardenafil dose should not surpass 5mg, whereas the dose of itraconazole and ketoconazole – 200mg. In case of underlying risk for bleeding and aggravation of peptic ulcer, the medication may be taken only after clinical risk and benefit analysis.
- Levitra doesn’t influence bleeding either during monotherapy or in combination with acidum acetylsalicylicum.
- Levitra doesn’t enhance thrombocyte aggregation developed on the setting of other medications intake.
- Exceed of therapeutic dosage of vardenafil leads to insignificant enhancement of anti-platelet effect of sodium nitroferricyanide which is in fact a nitrogen oxide donor.
Vardenafil metabolism involves hepatic cytochrome P450 enzymes (isoenzymes CYP3A4, CYP3A5, CYP2C), the inhibitors of which may decrease vardenafil clearance to a greater or lesser extent. Therefore, the combination with strong CYP3A4 inhibitors (itraconazole, ketoconazole, ritonavir) may cause considerable vardenafil concentration increase in blood plasma.
In case of co-administration with vardenafil:
- Cimetidine (non-specific inhibitor of isoenzymes of P450 cytochrome system) in the dose of 400mg twice a day doesn’t influence maximal concentration in blood and area under the concentration-time curve of vardenafil (20mg);
- Erythromycin (500mg three times per day) increases vardenafil’s area under the concentration-time curve by four times in its dosage of 5mg and increases maximal concentration of vardenafil by three times.
- Ketoconazole (200mg) causes augmentation of vardenafil (in dose of 5mg) ten-fold and maximal concentration of the latter by four times.
- Indinavir (inhibitor of HIV proteases) in the dose of 800mg three times a day promotes to enhancement of vardenafil’s area under the concentration-time curve (10mg) by sixteen times and its maximal concentration – by 7 times (vardenafil concentration in blood plasma in 24 hours after the intake decreases up to 4% from its maximal concentration.
- Ritonavir is therapeutic dosage of 600mg prolongs elimination half-life of vardenafil twice (5mg) up to 25 hours, increases maximal concentration of vardenafil by 13 times and total daily indicator of the area under the concentration-time curve by 49 times.
- Nitroglycerin in the dose of 0,4mg taken sublingually in the period of 24min-1h after Levitra intake (10mg) doesn’t enhance its hypotensive action.
- Maalox (antacid, magnesium hydroxide or aluminum hydroxide) doesn’t influence indicators of area under the concentration-time curve and maximal concentration of vardenafil.
- Ranitidine (300mg per day) and cimetidine (800mg per day) do not impact on bioaccessibility of the medicine.
- Combination of 20mg of vardenafil and 3,5mg of glyburide does not impact the indicators of area under the concentration-time curve and maximal concentration of the both drugs.
- There is no pharmacodynamic and pharmacokinetic interaction in case of combination of 20mg of vardenafil and 25mg of warfarin.
- Co-administration of 20mg of Levitra and 50 or 30mg of nifedipine doesn’t cause any considerable pharmacokinetic action.
- Hypotensive action of ethanol taken in the dose of 500mg per 1 kg of patient’s weight will not increase on the setting of vardenafil intake (20mg).
- There is no medical interaction for combination with digoxin. Vardenafil pharmacokinetics is not influenced by angiotensin-converting enzyme inhibitors, acetylsalicylic acid, beta-adrenergic blocking agents, hypoglycemic (sulfonylurea medications, metformin), diuretics, weak inhibitors of CYP3A4.
- Effects on ability to drive and use machines. Patients whose activity is tightly connected with driving or operating machinery first should state the degree of individual reaction on Levitra action.