Cialis - instructions for use, dose, side effects, contraindications

Active substanceTadalafilTadalafil

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Dosage form: & nbspfilm-coated tablets

Composition:

One tablet contains:

For a dosage of 2.5 mg:

Kernel: active substance: tadalafil 2.5 mg;

auxiliary substances: lactose monohydrate 79.39 mg, lactose monohydrate (dried

spraying) 12.50 mg, giprolose 0.87 mg, giprolose (extra thin) 2.00 mg, sodium lauryl sulfate

0.35 mg, microcrystalline cellulose 18.75 mg, croscarmellose sodium 8.00 mg, magnesium stearate

(vegetable) 0.63 mg.

Sheath (film): opada yellow (32K12891) 6.87 mg [lactose monohydrate 2.75 mg, hypromellose

1.93 mg, titanium dioxide 1.56 mg, triacetin 0.60 mg, iron dye yellow oxide 0.02 mg, dye

iron oxide red 0.01 mg].

For a dosage of 5.0 mg:

Kernel: active substance: tadalafil 5.0 mg;

auxiliary substances: lactose monohydrate 109.65 mg, lactose monohydrate (dried

by spraying) 17.50 mg, giprolose 1.22 mg, giprolose (extra thin) 2.80 mg, sodium lauryl sulfate

0.49 mg, microcrystalline cellulose 26.25 mg, croscarmellose sodium 11.20 mg, magnesium stearate

(vegetable) 0.88 mg.

Sheath (film): opadraj yellow (Y-30-12863-A) 8.75 mg [lactose monohydrate 3.72 mg,

hypromellose 2.59 mg, titanium dioxide 1.54 mg, triacetin 0.74 mg, iron dye yellow oxide

0.16 mg].

Description:

Tablets 2.5 mg: almond-shaped tablets coated with a film coating of light orange-yellow color. On one side is engraved "C 2Yg ".

Tablets 5 mg: almond-shaped tablets covered with a film coating of light yellow color. On one side is engraved "C 5".

Pharmacotherapeutic group:Erectile dysfunction remedy, PDE-5 inhibitor.

ATX: & nbsp

G.04.B.E.08 Tadalafil

Pharmacodynamics:

Tadalafil is a reversible selective inhibitor of specific phosphodiesterase type 5 (PDE-5) cyclic guanosine monophosphate (cGMP). When sexual stimulation causes local release of nitric oxide, inhibition of PDE-5 with tadalafil leads to an increase in the concentration of cGMP in the cavernous body of the penis. The consequence of this is the relaxation of the smooth muscles of the arteries and the flow of blood to the tissues of the penis, which causes an erection. Tadalafil does not have an effect in the absence of sexual arousal.

Research in vitro showed that tadalafil is a selective inhibitor of PDE-5. PDE-5 is an enzyme found in the smooth muscles of the cavernous body, in the smooth muscles of the vessels of internal organs, in skeletal muscles, platelets, kidneys, lungs and the cerebellum. The effect of tadalafil on PDE-5 is more active than on other phosphodiesterases. Tadalafil is 10,000 times more potent for PDE-5 than for PDE-1, PDE-2, PDE-4 and PDE-7, which are located in the heart, brain, blood vessels, liver, leukocytes, skeletal muscles and in other organs. Tadalafil 10,000 times more actively blocks PDE-5 than PDE-3 - an enzyme that is found in the heart and blood vessels. This selectivity for PDE-5 in comparison with PDE-3 is important, since PDE-3 is an enzyme involved in contraction of the heart muscle. Besides, tadalafil approximately 700 times more active in relation to PDE-5 than in relation to PDE-6, found in the retina and is responsible for photo transmission. Tadalafil also exhibits an effect of 9000 times more potent on PDE-5 than its effect on PDE-8, PDE-9 and PDE-10, and 14-fold more potent for PDE-5 compared with PDE-11.The distribution in tissues and the physiological effects of the inhibition of PDE-8-PDE-11 have not yet been elucidated.

Tadalafil improves an erection and increases the possibility of a full sexual intercourse.

Tadalafil in healthy individuals does not cause a significant change in systolic and diastolic pressure in comparison with placebo in the lying position (the average maximum decrease is 1.6 / 0.8 mm Hg, respectively) and in the standing position (the average maximum decrease is 0, 2 / 4.6 mm Hg, respectively). Tadalafil does not cause a significant change in the heart rate.

Tadalafil does not cause changes in color recognition (blue / green), which is explained by its low affinity for PDE-6. In addition, there is no effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size.

To assess the effect of daily administration of tadalafil on spermatogenesis, several studies have been carried out. None of the studies showed an undesirable effect on the morphology of spermatozoa and their mobility. In one study, a decrease in the average concentration of spermatozoa was found compared with placebo.Reducing the concentration of spermatozoa was associated with a higher incidence of ejaculation. In addition, there was no adverse effect on the average concentration of sex hormones, testosterone, luteinizing hormone, and follicle-stimulating hormone when taking tadalafil compared with placebo.
Efficacy and safety of the drug Cialis® (in doses of 2.5 mg, 5.0 mg) was studied in clinical trials. There was an improvement in erection in patients with erectile dysfunction of all severity levels when taking tadalafil once a day. In studies of primary efficacy, 5 mg of tadalafil, 62% and 69% of attempts at intercourse were successful compared with 34% and 39% of patients taking placebo. Taking 5 mg of tadalafil significantly improved erectile function within 24 hours between doses.

Pharmacokinetics:

Suction

After ingestion tadalafil quickly absorbed. The average maximum concentration (C max) in plasma is reached on average 2 hours after ingestion.

The speed and degree of absorption of tadalafil does not depend on the intake of food, so the drug Cialis® can be used regardless of the meal.The time of reception (in the morning or in the evening) had no clinically significant effect on speed and degree of absorption. The pharmacokinetics of tadalafil in healthy individuals is linear in time and dose. In the dose range of 2.5 to 20 mg, the area under the concentration-time curve (AUC) increases in proportion to the dose. Equilibrium concentrations in the plasma are reached within 5 days after taking the drug once a day.

The pharmacokinetics of tadalafil in patients with an erection disorder is similar to the pharmacokinetics of a drug in persons without erectile dysfunction.

Distribution

The average volume of distribution is about 63 liters, which indicates that tadalafil is distributed in the tissues of the body. In therapeutic concentrations, 94% of tadalafil in the plasma binds to proteins. Binding to proteins does not change with impaired renal function.

In healthy individuals, less than 0.0005% of the administered dose is found in the sperm.

Metabolism

Tadalafil is mainly metabolized with the participation of isoenzyme CYP3A4 cytochrome P450. The main circulating metabolite is methylcatechol glucuronide. This metabolite is at least 13,000 times less active against PDE-5 than tadalafil. Consequently, the concentration of this metabolite is not clinically significant.

Excretion

In healthy individuals, the average clearance of tadalafil when ingested is 2.5 l / h, and the average half-life is 17.5 hours. Tadalafil is excreted mainly in the form of inactive metabolites, mainly with feces (about 61% of the dose) and, to a lesser extent, with urine (about 36% of the dose).

Special Populations Elderly patients

Healthy elderly patients (65 years and over) had a lower clearance of tadalafil when ingested, which was expressed by an increase in the area under the concentration-time curve by 25% compared with healthy individuals aged 19 to 45 years. This difference is not clinically significant and does not require dose selection.
Patients with renal insufficiency
In patients with mild and moderate renal insufficiency, dose adjustment is not required. In connection with the increased exposure of tadalafil (AUC), patients with severe renal failure are not recommended Cialis®.
Patients with hepatic insufficiency
The pharmacokinetics of tadalafil in people with mild to moderate liver failure is comparable to that of healthy individuals.For patients with severe hepatic insufficiency (class C according to the Child-Pugh classification), no data are available. When appointing Cialis® patients with severe hepatic insufficiency should first assess the risk and benefits of using the drug.
Patients with diabetes mellitus
In patients with diabetes mellitus against the background of tadalafil, the area under the concentration-time curve was less by about 19% than in healthy individuals. This difference does not require a dose adjustment.

Indications:

erectile disfunction

Contraindications:

- Hypersensitivity to tadalafil or to any substance included in the preparation;

- In case of taking drugs containing any organic nitrates;

- Use in persons under 18 years of age;

- The presence of contraindications to sexual activity in patients with diseases of the cardiovascular system: myocardial infarction during the last 90 days, unstable angina, the onset of angina pectoris during intercourse, chronic heart failure II-IV Classes by classification NYHA, uncontrolled arrhythmias, arterial hypotension (blood pressure less than 90/50 mm Hg), uncontrolled hypertension, ischemic stroke during the last 6 months;

- Loss of vision due to non-arterial anterior ischemic neuropathy of the optic nerve (regardless of the connection with the intake of PDE-5 inhibitors);

- Simultaneous reception of doxazosin, as well as drugs for the treatment of erectile dysfunction;

- Often (more than 2 times a week) use in patients with chronic renal failure (creatinine clearance less than 30 ml / min);

- Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:

Since there is no data for patients with severe hepatic impairment (Child-Pugh class C), caution should be exercised in prescribing the drug Cialis® this group of patients.

Care should be taken when prescribing the drug Cialis® patients taking alpha1-adrenoblockers, because simultaneous use can lead to symptomatic arterial hypotension in some patients. In a study of clinical pharmacology, 18 healthy volunteers a single dose of tadalafil, symptomatic arterial hypotension was not observed with simultaneous administration of tamsulosin, alpha-1A-adrenoblocker."Interaction with other drugs").

Diagnosis of erectile dysfunction should include the identification of a potential underlying cause, appropriate medical examination and determination of treatment tactics.

Cialis® should be used with caution in patients with predisposition to priapism (in sickle cell anemia, multiple myeloma or leukemia) or in patients with anatomical deformation of the penis (angular curvature, cavernous fibrosis or Peyronie's disease). Also, use caution when taken with powerful inhibitors of the isoenzyme CYP3A4 (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), hypotensive drugs.

Pregnancy and lactation:

A drug Cialis® not suitable for use in women.

Dosing and Administration:

For ingestion.

For patients with frequent sexual activity (more than twice a week): recommended intake frequency - daily, once a day 5 mg, at the same time, regardless of food intake. The daily dose can be reduced to 2.5 mg, depending on the individual sensitivity.

For patients with infrequent sexual activity (less than twice a week): the administration of the drug is recommended Cialis® in a dose of 20 mg, immediately before sexual activity according to the instructions for the medical use of the drug. The maximum daily dose of the drug Cialis® is 20 mg.

Side effects:

Adverse events associated with taking tadalafil are usually minor or medium in severity, transient and decreased with continued use of the drug.

The most frequent (> 1%, <10%) adverse events are headache and dyspepsia, as well as back pain, myalgia, blood flushes to the face, nasal congestion.

Spontaneous (post-marketing) data

Adverse reactions occurring more often than in single cases are listed according to the following gradation: very often (> 10%); often (> 1%, <10%); infrequently (> 0.1%, <1%); rarely (> 0.01%, <0.1%); very rarely (<0.01%), it is not known (it is impossible to estimate the frequency of occurrence of reactions according to available data).

Disorders from the cardiovascular system:

Infrequently (> 0.1%, <1%): heart palpitations¹, tachycardia¹, lowering blood pressure, (in patients who have already taken antihypertensive drugs), increasing blood pressure Rarely (> 0.01%, <0.1%): myocardial infarction¹

It is not known (it is impossible to estimate the frequency of occurrence of reactions according to available data): unstable angina¹Impaired nervous system: Very often (> 10%): headache Often (> 1%, <10%): dizziness Rarely (> 0.01%, <0.1%): Syncope, migraine, transient ischemic attacks, stroke Disorders from the organs of vision: Infrequently (> 0.1%, <1%): blurred vision Rarely (> 0.01%, <0.1%): violation of visual fields
It is not known (it is impossible to estimate the frequency of occurrence of reactions according to available data): non-arterial anterior ischemic optic optic neuropathy, retinal vein occlusion
Disturbances from the respiratory system: Infrequently (> 0.1%, <1%): nose bleed Disorders from the digestive system: Often (> 1%, <10%): abdominal pain
Infrequently (> 0.1%, <1%): gastroesophageal reflux
Disturbances from the skin and subcutaneous tissue: Infrequently (> 0.1%, <1%): rash, hives, hyperhidrosis (increased sweating) It is not known (it is impossible to estimate the frequency of occurrence of reactions according to available data): Stevens-Johnson syndrome and exfoliative dermatitis
Common violations: Infrequently (> 0.1%, <1%): chest pain¹Rarely (> 0.01%, <0.1%): edema of the face It is not known (it is impossible to estimate the frequency of occurrence of reactions according to available data): sudden cardiac death¹Immune system disorders: Infrequently (> 0.1%, <1%): hypersensitivity reactions Disorders from the reproductive system: Rarely (> 0.01%, <0.1%): prolonged erection It is not known (it is impossible to estimate the frequency of occurrence of reactions according to available data): priapism ⁽¹⁾ They were observed in patients who previously had cardiovascular risk factors. However, it is impossible to determine precisely whether these phenomena are directly related to these risk factors, with tadalafil, with sexual arousal, or with a combination of these or other factors.

Overdose:

With a single appointment of healthy individuals tadalafil in a dose of up to 500 mg and patients with erectile dysfunction - repeatedly up to 100 mg / day, the undesirable effects were the same as with the use of lower doses. In case of an overdose, standard symptomatic treatment should be performed. With hemodialysis tadalafil almost not output.

Interaction:

The effect of other drugs on tadalafil

Tadalafil is mainly metabolized with the participation of isoenzyme CYP3A4. Selective inhibitor of isoenzyme CYP3A4 ketoconazole (400 mg per day) increases exposure

single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketoconazole (200 mg per day) increases the exposure of a single dose of tadalafil (AUC) by 107% and Cmax by 15% relative to AUC and Cmax values for only one tadalafil.

Ritonavir (200 mg twice daily), inhibitor of isoenzymes CYP3A4, 2С9, 2С19 and 2D6, increases exposure of a single dose of tadalafil (AUC) by 124% without changing Cmax. Although specific interactions have not been studied, it can be assumed that other HIV protease inhibitors, such as, for example, saquinavir, as well as inhibitors of isoenzyme CYP3A4, such as erythromycin and intraconazole, increase the activity of tadalafil.

Selective inductor of isoenzyme CYP3A4, rifampicin (600 mg per day), reduces the exposure of a single dose of tadalafil (AUC) by 88% and Stakh by 46%, relatively AUC and the values of Stach for only one tadalafil. It can be assumed that the simultaneous use of other isoenzyme inducers CYP3A4 also should reduce the concentration of tadalafil in plasma.

Simultaneous reception of the antacid (magnesium hydroxide / aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the area under the pharmacokinetic curve for tadalafil.

An increase in the pH of the stomach as a result of the administration of blockers of H2-histamine receptors of nizatidine did not affect the pharmacokinetics of tadalafil.

The safety and efficacy of the combination of tadalafil with other treatments for erectile dysfunction have not been studied, so the use of such combinations is not recommended.

Tadalafil does not potentiate the increase in bleeding time caused by the intake of acetylsalicylic acid.

Effect of tadalafil on other drugs

It is known that tadalafil strengthens the hypotensive effect of nitrates. This occurs as a result of the additive effect of nitrates and tadalafil on the metabolism of nitric oxide II (NO) and cGMP. Therefore, the use of tadalafil against the background of taking nitrates is contraindicated.

Tadalafil does not have a clinically significant effect on the clearance of drugs, metabolism which occurs with the participation of cytochrome P450. The studies confirmed that tadalafil Does not inhibit or induce isoenzymes CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP2E1.


	Tadalafil does not have a clinically significant effect on the pharmacokinetics S-warfarin or R/ RTI & gt; Tadalafil does not affect the effect of warfarin on prothrombin time.

Tadalafil does not increase the duration of bleeding caused by acetylsalicylic acid.

Tadalafil has systemic vasodilating properties and can enhance the effect of antihypertensive drugs aimed at lowering blood pressure. In addition, in patients taking several antihypertensive drugs in whom hypertension was poorly controlled, a slightly greater decrease in blood pressure was observed. In the vast majority of patients, this decrease was not associated with hypotensive symptoms. Patients receiving treatment
antihypertensive drugs and taking tadalafil, appropriate clinical recommendations should be given.

There was no significant reduction in blood pressure when tadalafil was used by persons who took selective alpha-blocker tamsulosin. The simultaneous use of tadalafil with doxazosin is contraindicated. When using tadalafil by healthy volunteers who took doxazosin (4-8 mg per day), alpha-adrenoblocker, increased antihypertensive effect of doxazosin. Some patients experienced dizziness. Fainting was not observed. The use of doxazosin in lower doses has not been studied.

Tadalafil did not affect the concentration of alcohol, nor did alcohol influence the concentration of tadalafil. At high doses of alcohol (0.7 g / kg), taking tadalafil did not cause a statistically significant decrease in the average blood pressure. In some patients, postural dizziness and orthostatic hypotension were observed. When taking tadalafil in combination with lower doses of alcohol (0.6 g / kg), a decrease in blood pressure was not observed, and dizziness occurred with the same frequency as when taking one alcohol.

Tadalafil does not have a clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.

Special instructions:

Sexual activity has a potential risk for patients with cardiovascular disease. Therefore, the treatment of erectile dysfunction, including with the drug Cialis®, should not be performed in men with heart diseases in which sexual activity is not recommended.

There are reports of the occurrence of priapism in the use of PDE-5 inhibitors, including tadalafil. Patients should be informed of the need to seek immediate medical attention in the event of an erection lasting 4 hours or more.Untimely treatment of priapism leads to damage to the tissues of the penis, resulting in irreversible impotence.

Safety and efficacy of the drug combination Cialis® with other types of treatment, violations have not been studied. Therefore, the use of such combinations is not recommended. Like other PDE-5 inhibitors, tadalafil has systemic vasodilator properties, which can lead to a transient decrease in blood pressure. Before prescribing the drug Cialis® doctors should carefully consider whether patients with cardiovascular disease will be exposed to undesirable effects due to such vasodilating effects.

Non-arterial anterior ischemic optic neuropathy (NAPION) is the cause of visual impairment, including complete loss of vision. There are rare post-marketing reports on cases of development of NAPION, in time associated with the intake of PDE-5 inhibitors. It is currently impossible to determine whether there is a direct link between the development of NAPION and the intake of PDE5 inhibitors or other factors.Doctors should recommend patients in case of sudden loss of vision stop taking tadalafil and seek medical help. Doctors should also tell patients that people who have undergone NAPION have a higher risk of re-developing NAPION.

Effectiveness of the drug Cialis® in patients who have undergone surgery on the pelvic organs or radical neuroserving prostatectomy, is unknown.

Effect on the ability to drive transp. cf. and fur:Despite the fact that the incidence of dizziness against a background of placebo and tadalafil is the same, during the treatment period it is necessary to be cautious when driving vehicles and taking other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated 2.5 mg, 5 mg.

For 14 tablets in a blister, consisting of aluminum laminated foil and PVC / PE / PCTFE film. For 1 or 2 blisters, together with the instructions for use, put in a pack of cardboard.

Packaging:(14) - blister (1) / Tablets, film-coated 5 mg.For 14 tablets in a blister, consisting of aluminum laminated foil and PVC / PE / PCTFE film. 1 blister, along with instructions for use, put in a cardboard package. / - cardboard package
(14) - blister (2) / Tablets, film-coated 5 mg. For 14 tablets in a blister, consisting of aluminum laminated foil and PVC / PE / PCTFE film. 2 blisters along with instructions for use are put in a cardboard package. / - cardboard package

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000133

Date of registration:11.01.2011

The owner of the registration certificate:Eli Lilly East SAEli Lilly East SA Switzerland

Manufacturer: & nbsp

LILLY DEL CARIBE, Inc. Puerto Rico

Representation: & nbspELI LILLY EAST SA ELI LILLY EAST SA Switzerland

Information update date: & nbsp30.08.2015

Illustrated instructions

Instructions

Cialis® (Cialis®)