Expiration date: 09/2025
The composition and form of issue:
Tablets, film-coated. 1 tablet contains:
tadalafil 5 or 20 mg
excipients: lactose monohydrate, croscarmellose sodium, hydroxypropyl cellulose, MCC, sodium lauryl sulfate and magnesium stearate, the mixture of the dye Opadry II yellow
in packages contour cell 1 or 2 PCs. in cardboard pack 1, 2 or 4 packs.
Pharmacokinetics:
Suction. After oral tadalafil is rapidly absorbed. Cmax is reached after an average of 2 h. the Rate and extent of absorption do not depend on food intake. The time of dosing (morning or evening) has no clinically significant effect on the rate and extent of absorption.
The pharmacokinetics of tadalafil at healthy persons is linear in regard to time and dose. In the dose range of 2.5 to 20 mg AUC increases proportionally with dose. CSS in plasma are attained within 5 days while taking the drug 1 time/day.
The pharmacokinetics of tadalafil in patients with dysfunction of the erection similar to the pharmacokinetics of the drug in individuals without the dysfunction of erection.
Distribution. Average apparent volume of distribution (Vd) is approximately 63 litres, indicating that tadalafil is distributed in body tissues. At therapeutic concentrations 94% of tadalafil bound to plasma proteins. In healthy persons less than 0.0005% of administered dose detected in semen.
Metabolism. Metabolized with the participation of isoenzyme CYP3A4. The major circulating metabolite is methylethanolamine. It is 13,000 times less active against PDE5 than tadalafil. Therefore, this metabolite is unlikely to be clinically significant.
Excretion. In healthy individuals the average clearance of tadalafil ingestion is 2.5 l/h, and the average T1/2 of 17.5 hours Tadalafil is excreted predominantly as inactive metabolites, mainly with feces (about 61%) and, to a lesser extent in the urine (approximately 36%).
Pharmacokinetics in special clinical cases
Healthy elderly (65 and over) have lower clearance of tadalafil, which was reflected in the increase in AUC by 25% compared with healthy individuals aged 19 to 45 years. This difference is not clinically significant and does not require dose adjustment.
In patients with renal insufficiency, including patients on hemodialysis, the AUC is greater than in healthy. protein Binding does not change when the impairment of renal function.
The pharmacokinetics of tadalafil in patients with mild or moderate hepatic insufficiency is comparable to that in healthy subjects. In patients with severe hepatic insufficiency (class C according to child-Pugh) data are not available.
In patients with diabetes mellitus on the background of the use of tadalafil AUC was lower by about 19% than in healthy individuals. This difference is not clinically significant and does not require changing the dose.
Description pharmacological action:
Is a reversible selective inhibitor of cyclic quasimonopoly-specific phosphodiesterase type 5 (cGMP-PDE5). When sexual stimulation causes local release of nitric oxide, inhibition of PDE5 tadalafil leads to increased levels of cGMP in the cavernous body of penis. The result is relaxation of smooth muscles of arteries and blood flow to the tissues of the penis that causes erections. Tadalafil has no effect without sexual stimulation.
Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 — an enzyme found in smooth muscles of the cavernous body vascular smooth muscle of internal organs, skeletal muscle, platelets, kidney, lung, cerebellum.
The action of tadalafil on PDE5 is more active than other phosphodiesterase. Tadalafil in 10,000 times more active against PDE5 than for PDE1, PDE2, PDE4, PDE7, which are localized in heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil in 10,000 times more active blocks PDE5 than PDE3 the enzyme that is found in the heart and blood vessels. This selectivity concerning PDE5 compared to PDE3 is important because PDE3 is an enzyme participating in the reduction of cardiac muscle. In addition, tadalafil about 700 times more active against PDE5 than for PDE6 found in the retina and is responsible for photoperiodic.
Tadalafil is also showing the action in 9000 times more potent against PDE5 compared to its effect on PDE8, 9, 10, and 14-fold more potent against PDE5 compared to PDE11. Tissue distribution and physiological effects of inhibiting PDE8–PDE11 so far not been elucidated.
Cialis improves erection and the possibility of successful sexual intercourse.
The drug acts within 36 hours the Effect is already apparent 16 minutes after ingestion in the presence of sexual arousal.
Tadalafil in healthy individuals does not cause significant changes in SBP and DBP compared to placebo in the lying position (mean maximum reduction is 1.6/0.8 mm Hg.St. respectively) and standing (mean maximum decrease of 0.2/4.6 mm Hg.St. respectively). Tadalafil does not cause significant changes in heart rate.
Tadalafil does not cause changes in color recognition (blue/green), due to its low affinity to PDE6. In addition, no marked effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size.
Tadalafil does not cause changes in testosterone, LH and FSH in blood plasma.
In placebo-controlled studies there were no clinically significant influence on the characteristics of sperm in men taking tadalafil in daily doses for 6 months.
Indications:
Erectile dysfunction.
Contraindications:
- hypersensitivity to the drug
- simultaneous reception of the preparations containing any organic nitrates
- use in individuals under the age of 18 years.
Application of pregnancy and breast-feeding:
The drug is not intended for use in women.
Side effects:
Most frequently: headache (11%), dyspepsia (7%).
Side effects are usually mild or moderate in severity, transient and diminish with continued dosing.
Possible back pain, myalgia, nasal congestion, tides blood to a person.
Seldom — swelling of eyelids, eye pain, conjunctival hyperemia, dizziness.
Very rarely — hypersensitivity reactions (including rash, urticaria and facial edema, Stevens-Johnson syndrome and exfoliative dermatitis) hypotension (in patients who are already taking antihypertensive agents), hypertension and syncope abdominal pain and gastroesophageal reflux hyperhidrosis (excessive sweating) priapism and delayed erection and blurry vision, partitially anterior ischemic neuropathy of the optic nerve, Central retinal vein occlusion, impaired visual field.
From the side of cardiovascular system: patients with cardiovascular risk factors myocardial infarction, sudden cardiogenic death, stroke, chest pain, palpitations and tachycardia. However, it is impossible to pinpoint whether these phenomena directly with these risk factors, tadalafil, sexual stimulation, or a combination of these or other factors.
Drug interactions:
The effect of other drugs on tadalafil
Tadalafil is mainly metabolized with the participation of the enzyme CYP3A4. Selective inhibitor of CYP3A4 ketoconazole in the dose 400 mg/day increases the AUC of tadalafil in a single dose by 312% and Cmax by 22%, and ketoconazole in dose 200 mg/day increases the effects of tadalafil, taken in a single dose of 107% and Cmax by 25%, relative to the AUC and Cmax values for only one of tadalafil.
Ritonavir (200 mg 2 times/day), an inhibitor of CYP3A4, 2C9, 2C19 and 2D6, increases the impact of a single dose of tadalafil (AUC) on 524% without change in Cmax. Despite the fact that the specific interactions has not been studied, it can be assumed that such protease inhibitors as ritonavir and saquinavir, and inhibitors of CYP3A4, such as erythromycin and Itraconazole, increase the activity of tadalafil.
Selective CYP3A4 inducer rifampin (rifampicin, 60 mg/sut) reduces the effects of a single dose of tadalafil (AUC) by 88% and Cmax by 46% relative to the AUC and Cmax values for only one of tadalafil. It is assumed that simultaneous administration of other CYP3A4 inducers should also reduce the concentration of tadalafil in plasma.
The simultaneous administration of antacid (magnesium hydroxide/aluminium hydroxide) and tadalafil reduced the rate of absorption of the latter without changing the AUC.
Increasing the pH of gastric juice as a result of receiving blocker histamine H2-receptor nizatidine has no effect on the pharmacokinetics of tadalafil.
The effect of tadalafil on other drugs
Tadalafil enhances the hypotensive effect of nitrates. This is the result of the additive action of nitrates and tadalafil on the metabolism of nitric oxide and cGMP. Therefore, the appointment of Cialis on the background of nitrates contraindicated.
Tadalafil has no clinically significant effect on clearance of drugs, metabolism which takes place with the participation of isoenzymes of cytochrome P450. Studies have confirmed that tadalafil does not inhibit and does not induce isozymes CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9, CYP2C19.
Tadalafil has no clinically meaningful effect on the pharmacokinetics of S-and R-warfarin. Tadalafil does not affect the action of warfarin in relation to PV.
Tadalafil does not increase the duration of bleeding on the background of the action of acetylsalicylic acid.
Tadalafil has a systemic vasodilating properties and may increase the effects of antihypertensive drugs aimed at lowering blood pressure. Additionally, for patients with poorly controlled hypertension, taking several antihypertensive drugs, was observed a greater decrease in blood pressure. The vast majority of these patients reduction was not associated with hypotensive symptoms. Patients receiving treatment antigipertenzivnye drugs and receiving tadalafil, should be given appropriate clinical guidelines.
Did not observed a significant reduction of blood pressure when the use of tadalafil simultaneously with selective &alpha1A-blocker tamsulosin.
When using tadalafil in healthy volunteers who took alpha-1-blocker doxazosin (8 mg per day), there was an increase hypotensive effect of doxazosin. Some patients experienced dizziness. Cases of syncope were observed. Lower doses of doxazosin were not studied.
Tadalafil not affect the concentration of ethanol, as ethanol did not affect the concentration of tadalafil. At high doses of ethanol (0.7 g/kg) receiving of tadalafil did not cause a statistically significant reduction in the average BP values. Some patients experienced postural dizziness and orthostatic hypotension. With the introduction of tadalafil in combination with lower doses of ethanol (0.6 g/kg), hypotension was not observed, dizziness occurred with the same frequency that the admission of only one alcohol.
Tadalafil has no clinically significant effect on the pharmacokinetics and pharmacodynamics of theophylline.
Method of application and dose:
Inside, (at least 16 minutes before anticipated sexual activity).
The maximum recommended dose of Cialis is 20 mg. the Maximum recommended frequency of reception — 1 time/day.
Patients can carry out attempt of sexual intercourse at any time within 36 hours after taking the drug in order to establish the optimal response time to receive the drug.
Overdose:
In a single assignment to healthy volunteers at a dose of 500 mg/day and patients with erectile dysfunction multiple times, up to 100 mg/day, undesirable effects were the same as when using the drug in lower doses.
Treatment: conducting standard symptomatic therapy. In hemodialysis tadalafil practically displayed.
Special instructions:
Application for violations of liver function. Patients with impaired hepatic function a special dose adjustment is not required. Since there are no data of controlled clinical studies on safety and efficacy of the drug Cialis in patients with severe hepatic insufficiency (class C according to child-Pugh), to use the drug in these patients should be with caution and only when absolutely necessary.
Application for violations of renal function. Patients with impaired renal function (Cl creatinine is >30 ml/min) a special selection of dose not required. On the face of the treatment Cialis in patients with renal failure of moderate severity (Cl creatinine from 31 to 50 ml/min) were reported more often back pain compared to patients with renal insufficiency, mild (creatinine Cl — 51 to 80 ml/min) or healthy volunteers. Patients with Cl creatinine &le50 ml/min the drug should be administered with caution. Since there are no data of controlled clinical studies on safety and efficacy of the drug Cialis in patients with renal insufficiency, severe (creatinine Cl &le30 ml/min) to use the drug in these patients should be with caution and only when absolutely necessary.
Care should be taken when administering the drug Cialis to patients taking &alpha1-blockers, such as doxazosin, since simultaneous application in some cases can cause symptomatic hypotension. In the study of clinical pharmacology in 18 healthy volunteers took a single dose of tadalafil, there was no symptomatic hypotension while the introduction &alpha1A-adrenoblocker tamsulosin.
Sexual activity has a potential risk for patients with cardiovascular diseases. Therefore, treatment of erectile dysfunction, including with the use of the drug Cialis, should not be performed in men with such diseases of heart at which sexual activity is not recommended.
Be aware of the potential risk of complications during sexual activity in patients with diseases of the cardiovascular system:
- myocardial infarction within the last 90 days
- unstable angina or angina occurring during sexual intercourse
- chronic heart failure (II functional class and higher classification of NYHA), which developed in the last 6 months
- uncontrolled cardiac arrhythmia
-hypotension (BP <90/50 mm Hg.St.) or uncontrolled hypertension
- stroke, myocardial in the last 6 months.
Caution should be used Cialis in patients with predisposition to priapism (for example sickle cell anemia, multiple myeloma or leukemia) or in patients with anatomical deformation of the penis (such as angulation, cavernous fibrosis or Peyronie's disease).
The patient should be informed of the need for immediate treatment to the doctor in case of erection, continued for 4 h or more. Delays in treatment of priapism leads to tissue damage of the penis, as a result, may occur long-term loss of potency.
On the background of the drug Cialis cases of priapism were reported.
The safety and effectiveness of combination drug Cialis with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.
Like other PDE5 inhibitors, tadalafil has systemic vasodilatory properties that may cause transient decrease in blood pressure. Before the appointment of Cialis physicians should carefully consider whether patients with cardiovascular disease to be subjected to undesirable effects due to such vasodilatory effects.
Use in Pediatrics
The drug Cialis is not used in patients under 18 years of age.
Effects on ability to drive vehicles and management mechanisms
Special considerations do not exist.
Storage conditions:
(in original packaging).
