2010/06/19

Cialis



Composition, structure and packing

Tablets, film-coated yellow, almond-shaped, with the inscription "From 20" on one side.
1 tab.
Tadalafil 20 mg



Excipients: lactose monohydrate, croscarmellose sodium, gidroksipropiltsellyuloza, microcrystalline cellulose, sodium lauryl sulfate, magnesium stearate, a mixture of dye Opadry II yellow.

1 pc. - Blisters (1) - packs cardboard.

2 pcs. - Blisters (1) - packs cardboard.

4 pcs. - Blisters (1) - packs cardboard.

8 pcs. - Blisters (1) - bundle pasteboard.

Clinico-pharmacological group: Drug for treatment of erectile dysfunction. PDE-5 inhibitor

Registration № №:
Tab., cover. membranous sheath, 20 mg: 1, 2, 4 or 8 pieces. - P № 014761/01-2003, 17.02.03 outage

Pharmacological action

The drug for the treatment of erection. Is a reversible selective inhibitor of specific phosphodiesterase type 5 (PDE-5) cGMP. When sexual stimulation causes local release of nitric oxide, inhibition of PDE-5 tadalafilom 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 shown that tadalafil is a selective inhibitor of PDE-5. PDE-5 - an enzyme found in smooth muscles of cavernous bodies in the vascular smooth muscles of internal organs, skeletal muscle, platelets, kidney, lung cerebellum.

Effects of tadalafil for PDE-5 is more active than other phosphodiesterase. Tadalafil 10 000 times more active against PDE-5 than for FDE1, FDE2, FDE4, FDE7, which are located in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle and other organs. Tadalafil 10 000 times more active blocks PDE-5 than FDE3 - an enzyme that is found in the heart and blood vessels. This selectivity against PDE-5 compared with FDE3 is important, because FDE3 is an enzyme involved in the reduction of the heart muscle. In addition, tadalafil is approximately 700 times more active against PDE-5 than in respect FDE6 found in the retina and is responsible for fotoperedachu.

Tadalafil is also shown in action 9000 times more potent against PDE-5, compared with its effect on FDE8, 9 and 10 and 14 times more potent against PDE-5, compared with FDE11. Distribution in tissues and physiological effects of inhibition FDE8-FDE11 so far not been clarified.

Tadalafil improves erection and the possibility of successful sexual intercourse.

The drug acts within 36 h. The effect is manifested as little as 16 minutes after taking the drug in the presence of sexual stimulation.

Tadalafil in healthy individuals causes no significant change in systolic and diastolic blood pressure compared with placebo in the supine position (mean maximum decrease of 1.6/0.8 mm Hg, respectively) and standing (mean maximum decrease of 0.2/4.6 mm Hg, respectively ). Tadalafil does not cause significant change in heart rate.

Tadalafil does not cause changes in the recognition of color (blue / green), which explains its low affinity for FDE6. In addition, no marked effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size.

Tadalafil does not cause changes in the level of testosterone, LH and FSH in blood plasma.

There were no clinically significant effect on the characteristics of sperm in men taking tadalafil at daily doses over 6 months in placebo-controlled studies.

Pharmacokinetics

Absorption

After oral tadalafil is rapidly absorbed. C max achieved after an average of 2 hours speed and extent of absorption do not depend on the meal. Time of drug administration (morning or evening) has no clinically significant effect on the rate and extent of absorption.

Tadalafil pharmacokinetics in healthy individuals is linear with respect to time and dose. At doses ranging from 2.5 to 20 mg AUC increased proportionally to dose. C ss in plasma are attained within 5 days while taking the drug 1 times / day.

The pharmacokinetics of tadalafil in patients with erectile dysfunction is similar to the pharmacokinetics of the drug in patients without erectile dysfunction.

Distribution

The average V d is about 63 liters, indicating that tadalafil is distributed in the tissues of the body. At therapeutic concentrations, 94% tadalafil bound to plasma proteins. In healthy persons less than 0.0005% of the administered dose was found in semen.

Metabolism

Metabolised involving isoenzyme CYP3A4. The main circulating metabolite is metilkateholglyukuronid. He is 13000 times less active against PDE-5 than tadalafil. Therefore, this metabolite is unlikely to be clinically significant.

Withdrawal

In healthy individuals the average clearance of tadalafil ingestion of 2.5 l / h and an average T 1 / 2 - 17.5 hours Tadalafil appears mostly as inactive metabolites mainly in the faeces (61%) and to a lesser extent in the urine (about 36%).

Pharmacokinetics in special clinical situations

Healthy elderly (65 years and over) have lower clearance tadalafil, which was reflected in increased AUC by 25% compared with healthy people aged 19 to 45 years. This distinction is not clinically significant and does not require selection of a dose.

In patients with renal insufficiency, including patients on hemodialysis, AUC greater than in healthy individuals. Protein binding is not altered by disrupting kidney function.

The pharmacokinetics of tadalafil in patients with mild or moderate hepatic insufficiency comparable to that in healthy individuals. For patients with severe hepatic insufficiency (class C according to Child-Pugh scale) data are not available.

Patients with diabetes mellitus during treatment with tadalafil AUC was lower by about 19% lower than in healthy individuals. This distinction is not clinically significant and does not require changing the dose.

Statement
erectile dysfunction

Dosage regimen

Drugs are taken by mouth.

The recommended maximum dose of Cialis is 20 mg. The maximum recommended frequency of reception - 1 times / day.

Cialis take at least 16 minutes before the anticipated sexual activity.

Patients may attempt to carry out a sexual act at any time within 36 hours after taking the drug in order to establish the optimal response time to receive the drug.

Side effect

The most frequently: headache (11%), dyspepsia (7%).

Side effects are usually minor or medium severity, transient and diminish with continued treatment.

Perhaps: back pain, myalgia, nasal congestion, flushing of the face.

Rare: edema of the eyelids, eye pain, hyperaemia of conjunctiva, dizziness.

Very rare: hypersensitivity reactions (including rash, urticaria and face edema, Stevens-Johnson syndrome and exfoliative dermatitis), hypotension (in patients who have already received antihypertensive drugs), hypertension, syncope, abdominal pain and gastro-reflux, hyperhydrosis ( excessive sweating), and the delay erection priapism, blurred vision, nearterialnaya anterior ischemic optic neuropathy, retinal vein occlusion, the violation of fields of view.

Since the cardiovascular system: patients with cardiovascular risk factors - myocardial infarction, sudden cardiogenic death, stroke, chest pain, palpitations and tachycardia. However, it is impossible accurately to determine whether these phenomena directly with these risk factors, with tadalafilom, with sexual arousal, or with a combination of these or other factors.

Contraindications
simultaneous reception of preparations containing any organic nitrates
use in persons aged 18 years
Hypersensitivity to the drug's components

Application of pregnancy and breastfeeding

The product is not intended for use in women.

Application for violations of liver function

Patients with impaired renal function of the liver of a special selection of a dose is not required. Since there is no evidence of controlled clinical studies on safety and efficacy of Cialis in patients with severe hepatic insufficiency, and use the drug in this category of patients should take special caution and only when absolutely necessary.

Application for violations of renal function

Patients with impaired renal function (spacecraft more than 30 ml / min) of a special selection of a dose is not required. The treatment Cialis in patients with renal insufficiency moderately (QC from 31 to 50 ml / min) were observed more frequently of back pain compared to patients with renal insufficiency mild (QC from 51 to 80 ml / min) or healthy volunteers . Patients with CC less than 50 ml / min, the drug should be prescribed with caution. Since there is no evidence of controlled clinical studies on safety and efficacy of Cialis in patients with renal failure severe (CC less than 30 ml / min) used the drug in this category of patients should take special caution and only when absolutely necessary.

Cautions

Precautions should be prescribed to patients with severe hepatic insufficiency (class C according to Child-Pugh scale), since the data of controlled clinical studies on safety and efficacy of Cialis in this group of patients lacking.

Need care in prescribing Cialis to patients receiving α1-blockers, such as doxazosin, as the simultaneous application, in some cases can lead to symptomatic arterial hypotension. In a study of clinical pharmacology in 18 healthy volunteers who received a single dose of tadalafil were observed symptomatic arterial hypotension, while the introduction of α1-blocker tamsulosin.

The treatment Cialis in patients with renal insufficiency moderately (QC from 31 to 50 ml / min) were observed more frequently of back pain compared to patients with renal insufficiency mild (QC from 51 to 80 ml / min) or healthy volunteers . Patients with CC less than 50 ml / min, the drug should be prescribed with caution.

The sexual activity has a potential risk for patients with cardiovascular diseases. Therefore, treatment of erectile dysfunction, including using Cialis, you should not hold for men with heart disease, in which sexual activity is not recommended.

Keep in mind the potential risk of complications in 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 over the last 6 months
uncontrolled arrhythmias
hypotension (BP less than 90/50 mm Hg) or uncontrolled hypertension
stroke, transferred within the last 6 months

Precautions should be applied Cialis in patients with predisposition to priapism (eg sickle cell anemia, multiple myeloma or leukemia) or in patients with anatomical deformation of the penis (such as triangulation, cavernous fibrosis or Peyronie's disease).

Patient should be informed about the need for an immediate visit to a doctor in the event of an erection, lasting 4 hours or more. Delayed treatment for priapism causes damage to the tissues of the penis, as a result of this can occur a long-term loss of potency.

Against the background of the drug Cialis cases priapism were reported.

Safety and efficacy of a combination of Cialis with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.

As with other PDE-5 inhibitors, tadalafil has a systemic vasodilating properties, which can lead to transient blood pressure decrease. Prior to the appointment of Cialis physicians should carefully consider the question - not whether the patients with their existing cardiovascular disease subjected to unwanted effects due to these vasodilator effects.

Use in Pediatrics

Cialis is not used in patients younger than 18 years.

Effects on ability to drive vehicles and management mechanisms

Specific recommendations are not available.

Overdose

For a single appointment healthy volunteers at a dose of 500 mg / day and patients with erectile dysfunction - many times up to 100 mg / day, adverse effects were the same as when using the drug at lower doses.

Treatment: conducting standard symptomatic therapy. In hemodialysis tadalafil virtually no output.

Drug Interactions

The influence of other drugs on tadalafil

Tadalafil is mainly metabolized with the participation of the enzyme CYP3A4. Selective CYP3A4 inhibitor ketoconazole at a dose of 400 mg / day increases the AUC of a single dose of tadalafil in 312% and C max - 22%, and ketoconazole 200 mg / day increases the effects of tadalafil, taken in a single dose of 107% and C max - 25%, relative to the AUC and C max values for only one tadalafil.

Ritonavir (200 mg 2 times / day), an inhibitor of CYP3A4, 2C9, 2S19, and 2D6, increases the impact of a single dose of tadalafil (AUC) at 524% without changing the C max. Despite the fact that the specific interactions have not been studied, we can assume that protease inhibitors such as ritonavir and saquinavir, as well as inhibitors of CYP3A4, such as erythromycin and itraconazole, increase the activity of tadalafil.

Selective CYP3A4 inducer rifampin (rifampicin, 60/mg/sut), reduces the impact of a single dose of tadalafil (AUC) by 88% and C max by 46%, relative to the AUC and C max values for only one tadalafil. It is assumed that the simultaneous administration of other inducers of CYP3A4 should also reduce the concentration of tadalafil in plasma.

At the same time taking an antacid (magnesium hydroxide / aluminum hydroxide) and tadalafil reduced the rate of absorption of the latter without changing its AUC.

Increasing the pH of gastric juice as a result of receiving blocker histamine H 2-receptor nizatidina no effect on the pharmacokinetics of tadalafil.

Effect of tadalafil on other drugs

Tadalafil enhances the hypotensive effect of nitrates. This is due to the additive action of nitrates and tadalafil on the metabolism of nitric oxide and cGMP. Therefore, the appointment of Cialis during treatment with nitrates is contraindicated.

Tadalafil has no clinically significant effect on clearance of drugs, the metabolism of which occurs with the participation of cytochrome P 450 isozymes. Studies have confirmed that tadalafil does not inhibit or induce isozymes CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9, CYP2C19.

Tadalafil has no clinically significant effect on the pharmacokinetics of S-and R-warfarin. Tadalafil does not affect the action of warfarin with respect to prothrombin time.

Tadalafil does not increase the duration of bleeding on the background of acetylsalicylic acid.

Tadalafil has a systemic vasodilating properties and may exacerbate the effects of antihypertensive drugs to lower blood pressure. Additionally, patients taking several antihypertensive agents, in which hypertension, poorly controlled, were observed several large blood pressure reduction. The vast majority of these patients reduction was not associated with hypotensive symptoms. Patients receiving treatment antngipertenzivnymi drugs and receiving tadalafil, should be given appropriate clinical recommendations.

There were no significant BP reduction when using tadalafil simultaneously with the selective alpha 1 A-blocker tamsulosin.

When using tadalafil healthy volunteers who took alpha 1-blocker doxazosin (8 mg / day) were increased hypotensive effect of doxazosin. Some patients experienced dizziness. No cases of syncope were not observed. Lower doses of doxazosin were not studying.

Tadalafil did not affect the concentration of ethanol, as ethanol does not affect the concentration of Tadalafil. At high doses of ethanol (0.7 g / kg) receiving tadalafil did not cause a statistically significant decrease in the mean arterial pressure. Some patients showed 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, and dizziness occurred with the same frequency that the admission of only one alcohol.

Tadalafil has no clinically significant effect on pharmacokinetics and pharmacodynamics of theophylline.

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Drug prescription.

Terms and Conditions of storage

The product should be stored out of reach of children, in their original packaging at a temperature not above 30 ° C. Shelf life - 3 years.