Short description: Cialis online without prescription in Worldwide Pharmacies
Cialis is an erectile malfunction’s the medical cure’s remedy. The remedy presents oneself the reversible selective inhibitor of the specific phosphodiesterase the fifth type. The main active substance is Tadalafil. The matter doesn’t render the effectiveness under the sexual stimulation’s absence. Just the opposite under the presence last one it makes better the erection and secures the successful conduct of sexual act. The remedy operates during the 36 hours. The effect becomes apparent no longer than over sixteen minutes after medicament’s applying (under the sexual stimulation’s availability only). Besides it isn’t observed the Cialis’s influence on the visual acuity, electroretinogram, intraocular pressure and pupil’s size. Cialis 20mg 180 pills is the most widespread configuration of tablet’s realizing form. The remedy is intended for men only as opposed to Viagra which is also recommended for the women’s applying under the some conditions.
Cialis drug’s applying
The sexual dysfunction is one of the most widespread men’s ailments. Under this disease the person can’t visualize his male power during the sex act in full measure because the malfunction is accompanied with as full absence of erection as last one so weak that the sexual act can’t happened. The most of male individuals are faced with this sickness independently of their age. The widespread opinion is erroneously that the impotence threatens in advanced age only. From the problems with erection any man doesn’t insure. Cialis is absolutely new and effective medicament for the male potention’s improvement. The preparation’s action isn’t connected with the eating and alcohol beverage foods that are a big plus for the men. The medicant is also one of the most drugs from the category of men’s health that raises the erection more than twenty-four hours. It gives the male individuals the full liberty in the choice of the time for sex. Cialis has some essential advantages before the preparations from this class. The medicant is absorbed into blood very quickly. You can apply the remedy in each day time and before or after eating because it is always effective. The medicine continues to operate during thirty-six hours that is more than Viagra’s action. The drug practically hasn’t any side effects. People diseased in diabetes mellitus can use this preparation. The medicament is approved by the physicians all over the world. The medicant doesn’t call the addiction.
Realizing forms and dosages Cialis
The remedy works at the same principle as Viagra’s working, operating on the smooth muscular system of the penis’s vessels, raising the blood flow in genitals. But effect from the remedy’s active matter is more powerful than in Viagra. The obligatory condition for the erection’s beginning is sexual impulse’s presence. Cialis is taken inward not more than one time per day of 1 pill only. The daily dosage can’t exceed 20mg. Men younger than 18 years can’t apply the preparation.Our pharmacy suggests different views of drugs including this medicine.
Nonoperating effects Cialis pills
Before the starting of Cialis’s applying the male individuals have to consult with doctor. Under the preparation’s using it can appearance some slight indispositions such as headache, dyspepsia, pains in the back, myalgia, stuffiness in nose and blood “hot flushes” to the face. Sometimes it may be eyelid edema, ache in eyes, hyperemia of conjunctiva, giddiness. There are some symptoms under the overdosage such as aggravation of side effect’s evidence. Doesn’t apply the remedy under the hypersensitivity to the medicant and heart-vascular system’s sicknesses (raising arterial pressure, instable angina pectoris or stenocardia appearing during the sexual act, drug-corrected arterial hypertension and so on).
Cialis - instructions, indications, composition, side effects
- Composition
- Official form
- Pharmacological group
- Pharmacological properties
- Indications
- Contra-indications
- Interaction with other officinal remedies and other views of interaction
- Specifics of applying
- Application under the pregnancy and breast-feeding
- Capability to influence on the reaction speed under control by motor transport or other mechanisms
- Applying ways and dosing
- Overdose
- Side effects
- Keeping time
- Keeping conditions
- Package
- Analogs
Composition
Active ingredient: 1 tablet contains 20 mg of Tadalafil;
Excipients: lactose, croscarmellose sodium, hydroxypropyl cellulose, microcrystalline cellulose, sodium lauryl sulfate, magnesium stearate, others.
Official form
Tablets, film coated.
Pharmacological group
Tablets for the treatment of erectile dysfunction. ATC code G04B E08.
Pharmacological properties
Pharmacological.
Mechanism of action.
Tadalafil is a selective reversible inhibitor of cyclic guanosine monophosphate – specific phosphodiesterase type 5 (PDE-5). When sexual stimulation causes a local release of nitric oxide, inhibition of PDE 5 by Tadalafil produces elevated levels of cGMP in the corpus cavernosum. This leads to the relaxation of smooth muscles and blood flow to the tissues of the penis, thereby creating an erection. Tadalafil is inactive without sexual stimulation.
The effect of inhibiting the concentration of cGMP in the cavernous body is also observed in the smooth muscles of the prostate, the bladder and their vessels that carry blood to the above organs. Vascular relaxation, which occurs in this case, leads to an increase in blood perfusion and may cause a reduction in the symptoms of benign prostatic hyperplasia. These vascular effects can be supplemented by inhibition of the activity of the afferent nerves of the bladder and relaxation of the smooth muscles of the prostate and bladder.
Pharmacokinetics.
Tadalafil is well absorbed after ingestion. The maximum plasma concentration (C max) is reached on average 2:00 after administration. Bioavailability of Tadalafil after oral administration was not established.
The speed and extent of absorption of Tadalafil is independent of food intake, so Cialis can be taken with or without food. Dose time (morning or evening) had no clinically significant effect on the rate and extent of absorption.
Distribution. The average volume of distribution is approximately 63 liters, indicating that Cialis is distributed in the tissue. At therapeutic concentrations of 94% Tadalafil in plasma is associated with proteins. Protein binding is not affected by renal impairment.
Metabolism. Tadalafil is predominantly metabolized by the Z4-4 cytochrome P450 (CYP) isoform. The major circulating metabolite is methylcatechol glucuronide. This metabolite is 13,000 times less active against PDE-5 than Tadalafil. Thus, it is expected that the metabolite will exhibit clinical activity at concentrations that are observed.
Linearity / nonlinearity of pharmacokinetics. The pharmacokinetics of Tadalafil in healthy volunteers is linearly proportional to time and dose. In the dose range from 2.5 mg to 20 mg, the exposure increases in proportion to the dose. Permanent plasma concentration is reached within 5 days with a daily intake once a day.
The pharmacokinetics of the drug is the same in patients with erectile dysfunction and in patients without it.
Separate groups of patients.
Elderly people. Elderly healthy volunteers (65 years old and older) had low Tadalafil clearance values on ingestion, which resulted in a 25% increase in exposure compared with healthy volunteers aged 19-45 years. This age effect is not clinically significant and does not require dose adjustment.
Renal failure. In clinical pharmacology studies using a single dose of Tadalafil (5-20 mg), the exposure of Tadalafil almost doubled in patients with weak (creatinine clearance from 51 to 80 ml / min) or moderate (creatinine clearance from 31 to 50 ml / min) renal failure, as well as in patients with end-stage renal disease on dialysis. In patients on hemodialysis, the maximum plasma concentration (max) was 41% higher than in healthy volunteers. The effect of hemodialysis on the withdrawal of Tadalafil can be neglected.
Liver failure. Exposure of Tadalafil in patients with weak and moderate hepatic insufficiency is comparable to the exposure in healthy volunteers at a dose of 10 mg. The safety data for prescribing Cialis to patients with severe hepatic insufficiency is limited. In the case of Cialis, the physician should carefully assess individual preferences / risks. There are no data regarding use in a dose higher than 10 mg in patients with hepatic insufficiency.
Patients with diabetes. Exposure of Tadalafil in diabetic patients was about 19% lower than in healthy volunteers. This difference in exposure does not require dose adjustment.
Indications
Treatment of erectile dysfunction in adult males.
The drug is effective in the presence of sexual stimulation.
Cialis is not indicated for use in women.
Contra-indications
Hypersensitivity to Tadalafil or to any other component of the drug.
In clinical studies, Tadalafil discovered the property of enhancing the hypotensive effect of nitrates. Tadalafil is contraindicated in patients who use organic nitrates in any dosage form.
Cialis should not be used for men with heart disease for whom sexual activity is undesirable. Physicians should consider the potential cardiac risk associated with sexual activity in patients with cardiovascular diseases they already have.
The following groups of patients with cardiovascular diseases were not included in clinical trials, therefore Tadalafil use is contraindicated in them:
- patients with myocardial infarction in the last 90 days
- patients with unstable angina or angina, occurs during sexual intercourse;
- patients with heart failure, class 2 or higher;
- patients with uncontrolled arrhythmias, hypotension (<90/50 mmHg) or uncontrolled hypertension;
- patients after a stroke that occurred in the last 6 months.
The simultaneous use of PDE-5 inhibitors, including tadalafil, with guanylate cyclase stimulants, such as riociguat, is contraindicated, since this could potentially lead to symptomatic hypotension.
Interaction with other officinal remedies and other views of interaction
Interaction studies have been carried out for dosages of 10 mg and 20 mg, data are provided below. Clinically significant interaction at the use of high doses cannot be excluded, if such was observed when using Cialis in low doses (10 mg).
Effect of other drugs on Tadalafil.
Inhibitors of cytochrome CYP450.
Tadalafil is metabolized by CYP3A4. Selective CYP3A4 inhibitor – ketoconazole (200 mg daily) – increases the area under the curve «concentration-time» (AUC) of tadalafil (10 mg) by 2 times and C max by 15% relative to the AUC and C max values of tadalafil alone. Ketoconazole (400 mg per day) increases the area under the curve «concentration-time» (AUC) of tadalafil (20 mg) by 4 times and C max by 22%. Ritonavir, a protease inhibitor (200 mg twice daily), which inhibits CYP3A4, CYP2С9, 2С19 and CYP2D6, increases the area under the curve «concentration-time» (AUC) of tadalafil (20 mg) 2 times, without changing Cmax. Although specific interactions have been investigated, other protease inhibitors, such as saquinavir and other CYP3A4 inhibitors, such as erythromycin, clarithromycin, itraconazole and grapefruit juice, should be prescribed with caution because it is expected that when used together they will increase the concentration of tadalafil in plasma. As a result, the incidence of adverse reactions may increase.
Inductors of cytochrome CYP450.
CYP3A4 inductor rifampicin reduces the AUC value of tadalafil by 88% compared to the AUC value of tadalafil alone (10 mg). It can be assumed that such a decrease in concentration will reduce the effectiveness of tadalafil. The simultaneous use of other inducers of CYP3A4, such as phenobarbital, phenytoin and carbamazepine, can also reduce the concentration of tadalafil in plasma.
The effect of tadalafil on other drugs.
Nitrates. In clinical studies, tadalafil (5 mg, 10 mg, 20 mg) showed the ability to enhance the hypotensive effects of nitrates. Thus, the use of Cialis by patients receiving treatment with organic nitrates in any form is contraindicated. If for a patient who is destined to Cialis at any dose (2.5–20 mg), the use of nitrates is medically necessary in a life-threatening condition, then it should take at least 48 hours after the last use of Cialis. In this case, the use of nitrates should occur under control with proper monitoring of hemodynamic parameters.
Antihypertensive drugs (including calcium channel blockers).
During co-administration of tadalafil (5 mg once daily or as a single dose of 20 mg) with the α-adrenoreceptor blocker doxazosin (4-8 mg per day), the hypotensive effect of the latter was significantly increased. This effect lasts until 12:00 and can be manifested by individual symptoms, including in the form of dizziness. This combination of drugs is not recommended for use.
It should be carefully prescribed Cialis to patients who receive treatment with α-adrenoreceptor blockers, especially for elderly people. Treatment should begin with a minimum dosage and gradually increase the dose.
In the course of clinical pharmacodynamic studies, the potential of tadalafil to enhance the antihypertensive effects of the main antihypertensive drugs was studied. The main classes of drugs were studied: calcium channel blockers (amlodipine), ACE inhibitors (enalapril), β-adrenoreceptor blockers (metoprolol), thiazide diuretics (bendrofluazide) and angiotensin II receptor blockers (alone and in combination with thiazide diuretics, calcium blockers) β-adrenoreceptors and / or α-adrenoreceptor blockers). Tadalafil (at a dose of 10 mg, except for research on the interaction with angiotensin II receptor blockers and amlodipine, where the effect of a dose of 20 mg was studied) did not show significant interaction with the above classes of drugs. In another study of clinical pharmacology, the simultaneous use of tadalafil (at a dose of 20 mg) with several antihypertensive drugs (up to four) was studied. In patients taking several antihypertensive drugs, changes in blood pressure depended on the level of blood pressure control. Thus, in patients with well-controlled hypertension, the pressure decrease was insignificant and corresponded to that in healthy volunteers. In patients with difficult-to-control arterial hypertension, a greater reduction in blood pressure was observed, although in most patients the reduction in pressure was not accompanied by hypotensive symptoms. In patients receiving antihypertensive medication, the use of tadalafil at a dose of 20 mg can lead to a decrease in blood pressure, which (except for the simultaneous use of α-adrenoreceptor blockers) is insignificant and clinically insignificant. Analysis of the data of the third phase of the clinical study is not a manifestation of the difference in adverse reactions that occurred in patients treated with tadalafil with the concomitant use of antihypertensive drugs and treatment only with tadalafil. Despite this, it is necessary to provide appropriate recommendations for a possible reduction in blood pressure to patients who are treated with antihypertensive drugs and Cialis.
Riociguat.
In the course of preclinical studies, an additive hypotensive effect was detected while taking PDE-5 inhibitors with riociguat. In clinical studies, it was found that riociguat enhances the hypotensive effect of PDE inhibitors 5. There was no evidence of a favorable clinical effect of this combination in the studied population. Simultaneous use of riociguat with PDE-5 inhibitors, including tadalafil, is contraindicated.
5-α-reductase inhibitors.
In a clinical study that compared the combined use of tadalafil 5 mg and finasteride 5 mg with placebo and finasteride 5 mg to eliminate the symptoms of benign prostatic hyperplasia, no new adverse reactions were found. However, since there has been no study of drug interaction to evaluate the effects of tadalafil and 5-α-reductase inhibitors, it is advised to use Cialis with caution in patients who receive treatment with 5-α-reductase inhibitors.
Ethinyl estradiol and terbutaline.
Tadalafil increased the bioavailability of oral dosage forms with ethinyl estradiol. Such an increase in bioavailability can be expected when combined with terbutaline, although the clinical effects of this combination are unknown.
Alcohol.
Alcohol (average maximum concentration of 0.08%) did not affect the simultaneous use of tadalafil (at a dose of 10 or 20 mg). There was also no change in tadalafil concentration over the next three hours after taking alcohol with tadalafil at the same time. Alcohol was used in such a way as to achieve the maximum level of alcohol absorption (fast intake without food within 2:00 after application). Taking tadalafil (at a dose of 20 mg) would not lead to a statistically significant reduction in blood pressure while taking alcohol (0.7 g / kg), however, some patients experienced postural dizziness and orthostatic hypotension. Taking tadalafil on the background of lower doses of alcohol (0.6 g / kg) did not cause arterial hypotension, and dizziness was observed with the same frequency as when taking only alcohol. The effect of alcohol on cognitive functions did not increase with the simultaneous use of tadalafil (at a dose of 10 mg).
Drugs that are metabolized with the participation of cytochrome P-450.
Tadalafil is not expected to cause clinically significant inhibition or induction of clearance of drugs that are metabolized by CYP450 isoforms. In clinical studies, it has been proven that tadalafil is not inhibited and does not induce CYP450 isoforms, in vol. CH. CYPRA4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
CYP2C9 substrates (for example, R-warfarin).
Tadalafil (at a dose of 10 mg and 20 mg) showed no clinically significant effect on the exposure (AUC) of S-warfarin or R-warfarin (CYP2C9 substrates), and also had no effect on the prothrombin time induced by warfarin.
Aspirin.
Tadalafil (at a dose of 10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetylsalicylic acid.
Antidiabetic drugs.
Specific studies of the interaction of tadalafil with hypoglycemic drugs have not been conducted.
Specifics of applying
Before starting treatment Cialis.
Before using the drug, the doctor should determine the causes of erectile dysfunction and prescribe an appropriate course of treatment.
Before starting any treatment for erectile dysfunction, physicians should consider the state of the patient’s cardiovascular system, since there is a certain degree of cardiac risk associated with sexual activity. Tadalafil exhibits a vasodilating effect, which can lead to a slight and transient decrease in blood pressure and potentiation of the hypotensive effect of nitrates.
It is unknown whether Cialis is effective for patients who have undergone surgery on the pelvic bones or radical prostatectomy without preserving the nerves.
Cardiovascular system.
According to clinical studies serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina, ventricular arrhythmia, cerebral circulation, transient ischemic attack, chest pain, palpitations and tachycardia have been reported. Most patients who had such adverse reactions had risk factors for the cardiovascular system.
It is necessary to carefully prescribe Cialis to patients taking a-1 blockers, since in some patients the simultaneous use of these medications can lead to symptomatic hypotension. The combined use of tadalafil and doxazosin is not recommended.
Eye problems.
Cases of visual impairment and non-arterial anterior ischemic optic neuropathy (NAPION) have been reported with Cialis and other PDE-5 inhibitors. The doctor should warn the patient about the need to cancel tadalafil and seek medical help in case of sudden loss of vision.
Liver failure.
Clinical data on the safety of a single dose of Cialis for patients with severely impaired liver function (class C) are limited. When prescribing Cialis to such patients, the physician should carefully evaluate the individual preferences / risks of therapy.
Priapism and anatomical deformation of the penis.
Patients who have erections lasting 4:00 or more should be told to immediately seek medical attention. If priapism is not treated immediately, it can lead to damage to the tissues of the penis and long-term loss of potency.
It is necessary to carefully prescribe Cialis to patients with anatomical deformities of the penis (such as angular curvature, cavernous fibrosis or Peyronie’s disease) or patients who have conditions that can lead to priapism (such as sickle cell anemia, myeloma, or leukemia).
Simultaneous use with CYP3A4 inhibitors.
It is necessary to carefully prescribe Cialis ® to patients taking CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), because when used together with tadalafil, an increase in tadalafil (AUC) is observed.
Simultaneous use with other drugs for the treatment of erectile dysfunction.
The safety and efficacy of using Cialis in combination with other PDE-5 inhibitors or other agents for treating erectile dysfunction have been studied, so patients should be advised not to take Cialis in similar combinations.
Lactose.
Cialis contains lactose. Cialis should not be given to patients with rare hereditary forms of intolerance to galactose, glucose-galactose malabsorption syndrome.
Application under the pregnancy and breast-feeding
Cialis is not indicated for use in women.
Fertility. In two clinical studies, it was found that fertility disorders are not expected in humans, although a decrease in sperm concentration was observed in individual men.
Capability to influence on the reaction speed under control by motor transport or other mechanisms
The effect of Cialis on the ability to control machines and mechanisms is insignificant. Although the frequency of reports of dizziness during clinical trials with placebo and during clinical trials with tadalafil was similar, patients should know how Cialis affects them before driving vehicles or working with machinery.
Applying ways and dosing
For oral intake. For overdose patients should take tablets with the appropriate content of the active substance.
Adult men. The recommended dose is 10 mg before the intended sexual activity, regardless of the meal. Patients in whom tadalafil at a dose of 10 mg does not have the desired effect, you can apply a dose of 20 mg.
The drug is taken at least 30 minutes before the expected sexual activity. The effectiveness of tadalafil lasts up to 36 hours after administration.
The maximum recommended frequency of admission – once a day.
Tadalafil in a dose of 10 mg and 20 mg is intended for use before the intended sexual activity and is not recommended for daily use.
In the case of the alleged frequent use of Cialis (at least twice a week), the daily use of lower doses of preparation may be more appropriate, based on the choice of the patient and the decision of the doctor. For these patients, the recommended dose is 5 mg / day at about the same time. The dose can be reduced to 2.5 mg / day, based on the individual tolerance of the drug. The feasibility of long-term daily use should be periodically reviewed.
Special patient groups.
Older men. Dose adjustment is not required.
Men with renal failure. Dose adjustment is not required for patients with mild to moderate renal insufficiency. For patients with severe renal insufficiency, the maximum recommended dose is 10 mg, with the use of tablets of the appropriate dosage.
Men with liver failure. The recommended dose of Cialis is 10 mg before the intended sexual activity, regardless of the meal.
Clinical safety data for prescribing Cialis to patients with severe hepatic insufficiency (class C) is limited; in the case of an appointment, the physician should carefully evaluate individual preferences / risks. There are no data regarding the use of Cialis in a dose higher than 10 mg in patients with hepatic insufficiency. There is no data on the use of medicine at a dose of 2.5-5 mg once a day for patients with hepatic insufficiency, therefore, in the case of a prescription, the physician should carefully evaluate the individual preferences / risks of prescribing pills at a dose of 2.5-5 mg once a day.
Men with diabetes. Dose adjustment is not required.
Children. The drug is not intended for use in children.
Before using the drug, you should consult with your doctor and familiarize yourself with the annotation approved by the manufacturer. Information about the medication should not be used as a guide to self-treatment.
Overdose
Symptoms. With a single use of tadalafil in a dose of up to 500 mg by healthy volunteers and with repeated use of tadalafil up to 100 mg per day by patients, the side effects were similar to those observed when using smaller doses of the drug.
Treatment. In case of overdose, if necessary, standard symptomatic therapy should be applied. Hemodialysis did not significantly affect the elimination of tadalafil.
Side effects
Side effects, which are reported most often in the treatment of erectile dysfunction, are headache, dyspepsia, back pain, myalgia, the incidence of which increased with increasing doses of Cialis. Adverse reactions were brief, mild to moderate:
Immune system: infrequent hypersensitivity reactions, rarely angioedema.
Nervous system: often – headache, infrequently – dizziness, rarely – violation of cerebral circulation (including hemorrhagic phenomena), loss of consciousness, transient ischemic attack, migraine, convulsions, transient amnesia.
Organs of vision: infrequently – blurred vision, sensation of pain in the eyes, rarely – visual field defects, eyelid edema, conjunctiva hyperemia.
Organs of hearing: infrequently – ringing in the ears, rarely – sudden loss of hearing.
Heart: infrequently – tachycardia, palpitations, rarely – myocardial infarction, unstable angina, ventricular arrhythmia.
Vessels: often – hot flashes, infrequently arterial hypotension, arterial hypertension.
Respiratory system: often – nasal congestion, infrequently, shortness of breath, nosebleeds.
Gastrointestinal system: often – dyspepsia, infrequently – abdominal pain, nausea, vomiting, gastroesophageal reflux.
Skin and subcutaneous tissues: rarely – rash, rarely – urticaria, Stevens-Johnson syndrome, exfoliative dermatitis, hyperhidrosis (excessive sweating).
Musculoskeletal system, connective and musculoskeletal tissue: often – back pain, myalgia, pain in the limbs.
Renal and urinary system: infrequently – hematuria.
Reproductive system: infrequently – prolonged erection, rarely – priapism, hemorrhage from the penis, hemospermia.
Common disorders: infrequent – chest pain, peripheral edema, weakness, rarely – swelling of the face, sudden cardiac death.
Keeping time
3 years.
Keeping conditions
The drug should be stored in its original packaging at a temperature not higher than 30 ° C in the reach of children.
Package
1 or 2 tablets of 20 mg in a blister pack, 1, 2 or 4 blisters in a carton.
Analogs
Tadalafil
- Composition
- Official form
- Pharmacological group
- Pharmacological properties
- Indications
- Contra-indications
- Interaction with other officinal remedies and other views of interaction
- Specifics of applying
- Application under the pregnancy and breast-feeding
- Capability to influence on the reaction speed under control by motor transport or other mechanisms
- Applying ways and dosing
- Overdose
- Side effects
- Keeping time
- Keeping conditions
- Package
- Analogs