Tadalafil VERTEX 5mg

description

A remedy for the treatment of erectile dysfunction from the Vertex company.

 

Structure

Dosage 5 mg:

active substance: tadalafil 5,000 mg;

excipients: lactose monohydrate, microcrystalline cellulose 102, croscarmellose sodium, hyprolose (hydroxypropyl cellulose), magnesium stearate, talc, sodium lauryl sulfate;

film coating: [hypromellose, hyprolose (hydroxypropyl cellulose), talc, titanium dioxide, iron dye yellow oxide (iron oxide)] or [dry film coating mix containing hypromellose, hyprolose (hydroxypropyl cellulose), talc, titanium dioxide, iron dye yellow oxide (iron oxide)].

 

pharmachologic effect

Tadalafil is a reversible selective inhibitor of type 5 phosphodiesterase (PDE-5) specific to cyclic guanosine monophosphate (cGMP). When sexual arousal induces a local release of nitric oxide, inhibition of PDE5 by tadalafil leads to an increase in the concentration of cGMP in the corpus cavernosum of the penis. The consequence of this is relaxation of smooth muscles and blood flow to the tissues of the penis, which causes an erection. Tadalafil has no effect in the treatment of erectile dysfunction in the absence of sexual arousal.

 

Indications

- Erectile dysfunction;

- symptoms from the lower urinary tract in patients with benign prostatic hyperplasia (for a dosage of 5 mg);

- erectile dysfunction in patients with symptoms from the lower urinary tract in the presence of benign prostatic hyperplasia (for a dosage of 5 mg).

 

Method of administration and dosage

For oral administration.

Use of the drug as indicated erectile dysfunction (ED)

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

The appropriateness of the daily use of the drug should be periodically reviewed.

For patients with infrequent sexual activity (at least twice a week): the recommended dose of tadalafil is 20 mg, which are taken before the intended sexual activity, regardless of food intake.

The drug should be taken at least 30 minutes before sexual activity.

The maximum frequency of admission is once a day.

Tadalafil 20 mg is intended for use before the intended sexual intercourse, and is not recommended for continuous daily intake.

Use of the drug for BPH or ED / BPH

The recommended dose is 5 mg taken at about the same time every day, with or without food. For adult men undergoing treatment for both benign prostatic hyperplasia and erectile dysfunction, the recommended dose is also 5 mg taken at about the same time every day.

 

Special patient groups

Elderly patients

In elderly patients, dose selection is not required.

Renal failure

No dose adjustment is required in patients with mild to moderate renal impairment.

In patients with severe renal impairment, the maximum recommended dose when used on demand is 10 mg.

Daily intake of tadalafil in doses of 2.5 or 5 mg for the treatment of erectile dysfunction and benign prostatic hyperplasia is not recommended for patients with severe renal failure.

Liver failure

In the treatment of erectile dysfunction, the recommended dose of tadalafil is 10 mg, which is taken before the intended sexual activity, regardless of food intake. There are limited clinical data on the safety of tadalafil in patients with severe hepatic impairment (Child-Pugh class C); therefore, when prescribing this drug by the doctor, a careful individual assessment of the ratio of benefits and risks of its use should be carried out. There are no data on the use of tadalafil in patients with hepatic insufficiency in doses of more than 10 mg.

Daily use of tadalafil for the treatment of erectile dysfunction and benign prostatic hyperplasia in patients with hepatic impairment has not been evaluated; therefore, when prescribing this drug by the doctor, a careful individual assessment of the ratio of benefits and risks of its use should be carried out.

Diabetes

No dose adjustment is required in patients with diabetes mellitus.

 

Side effects

Immune system disorders:

infrequently - hypersensitivity reactions;

rarely - angioedema.

Nervous system disorders:

often - headache;

infrequently - dizziness;

rarely - stroke (including acute cerebrovascular accident (ACVA) of hemorrhagic type), fainting, transient ischemic attacks, migraine, epileptic seizures, transient amnesia.

Violations of the organ of vision:

infrequently - blurred vision, pain in the eyeball;

rarely - visual field disturbance, swelling of the eyelids, conjunctival hyperemia, non-arterial anterior ischemic optic neuropathy, occlusion of the retinal vessels.

Hearing and labyrinth disorders:

infrequently - ringing in the ears;

rarely - sudden hearing loss.

Heart disorders:

infrequently - tachycardia, palpitations;

rarely - myocardial infarction, ventricular arrhythmias, unstable angina pectoris.

Vascular disorders:

often - "hot flushes" of blood to the face;

infrequently - a decrease in blood pressure, an increase in blood pressure.

Respiratory, chest and mediastinal disorders:

often - nasal congestion;

infrequently - shortness of breath, nosebleeds.

Gastrointestinal disorders:

often - dyspepsia;

infrequently - abdominal pain, gastroesophageal reflux; diarrhea in patients over 65 years of age, nausea, vomiting.

Skin and subcutaneous tissue disorders:

infrequently - skin rash;

rarely - urticaria, Stevens-Johnson syndrome, exfoliative dermatitis, hyperhidrosis (excessive sweating).

Muscular, skeletal and connective tissue disorders:

often - back pain, myalgia, pain in the limbs.

Kidney and urinary tract disorders:

infrequently - hematuria.

Reproductive system and breast disorders:

infrequently - prolonged erection;

rarely - priapism, hematospermia, bleeding from the penis.

General disorders and reactions at the injection site:

infrequently - chest pain, peripheral edema, fatigue;

rarely - facial edema, sudden cardiac death.

Contraindications

- Hypersensitivity to tadalafil or to any substance that is part of the drug;

- in case of taking medications containing any organic nitrates. In clinical studies, it has been shown that tadalafil enhances the hypotensive effect of nitrates. This is believed to be due to the combined effects of nitrates and tadalafil on the nitric oxide / cGMP pathway;

- children up to age 18;

- the presence of contraindications to sexual activity in patients with diseases of the cardiovascular system. Physicians should consider the possible cardiac risk of sexual activity in patients with a history of cardiovascular disease. The following groups of patients with diseases of the cardiovascular system were not included in clinical trials, and therefore, taking tadalafil is contraindicated for them: patients with myocardial infarction within the last 90 days, patients with unstable angina pectoris or an attack of angina pectoris during intercourse, patients with chronic heart failure of class II and higher according to the NYHA classification within the last 6 months, patients with uncontrolled arrhythmias, arterial hypotension (BP less than 90/50 mm Hg), uncontrolled arterial hypertension, patients with a stroke within the last 6 months;

- loss of vision in one eye due to non-arterial anterior ischemic optic neuropathy (regardless of the connection with the previous intake of PDE-5 inhibitors);

- simultaneous use with doxazosin, with other PDE-5 inhibitors and other treatment options for erectile dysfunction; - simultaneous use with guanylate cyclase stimulants, such as riociguat, is contraindicated, since it can lead to symptomatic hypotension;

- use in patients with severe chronic renal failure (CC less than 30 ml / min);

- rare hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Overdose

With a single appointment to healthy volunteers of tadalafil at a dose of up to 500 mg and to patients with erectile dysfunction - repeatedly up to 100 mg / day, the undesirable effects were the same as when using lower doses.

In case of overdose, it is necessary to carry out standard symptomatic treatment. With hemodialysis, tadalafil is practically not excreted.

 

special instructions

Before you start taking Tadalafil

Before deciding on pharmacotherapy, it is necessary to collect a medical history and conduct a physical examination to diagnose erectile dysfunction or benign prostatic hyperplasia and determine the possible causes of their development.

Before starting any treatment for erectile dysfunction, doctors should consider the cardiovascular health of their patients, as there is a certain degree of cardiac risk associated with sexual activity. Tadalafil has vasodilating properties, which leads to a slight transient decrease in blood pressure and, thus, enhances the hypotensive effect of nitrates.

Before starting treatment with tadalafil BPH, patients should be examined to exclude the presence of prostate carcinoma, and a thorough assessment of the state of the cardiovascular system should be carried out.

Diagnosis of erectile dysfunction should include identification of the potential underlying cause, appropriate medical evaluation and treatment.

The efficacy of tadalafil in patients undergoing pelvic surgery or radical prostatectomy without preserving the neurovascular bundles is unknown.

The cardiovascular system

According to post-marketing surveillance and / or clinical studies, serious cardiovascular manifestations have been reported, including myocardial infarction, sudden cardiac death, unstable angina pectoris, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, palpitations, and tachycardia. Most of the patients who reported these manifestations had a history of cardiovascular risk factors. However, it is impossible to conclusively determine whether these phenomena are directly related to risk factors, taking tadalafil, sexual activity, or a combination of certain factors.

In patients receiving concomitant antihypertensive therapy, tadalafil may cause a decrease in blood pressure. Before starting the daily intake of tadalafil, you should consider the possibility of adjusting the dose of antihypertensive drugs.

In patients taking alpha1-blockers, concomitant use of tadalafil in some cases can lead to symptomatic hypotension. Taking tadalafil in combination with doxazosin is not recommended.

Vision

When taking tadalafil and other PDE-5 inhibitors, there were cases of visual impairment and the development of non-arterial anterior ischemic optic neuropathy (NAPION). Analysis of observational data indicates an increased risk of developing acute NAPION in men with erectile dysfunction after exposure to tadalafil or other PDE-5 inhibitors. As this applies to all patients receiving tadalafil, they should be advised that in case of sudden visual impairment, they should stop taking the drug and seek immediate medical attention.

Decreased or sudden hearing loss

Cases of sudden hearing loss have been reported following the use of tadalafil. Although in some cases other risk factors were present (such as age, diabetes mellitus, hypertension, and a history of hearing loss), it should be recommended to stop taking tadalafil and seek prompt medical attention in case of sudden hearing loss or loss.

Renal and hepatic impairment

Due to the increased AUC values, limited clinical experience and the lack of the ability to influence clearance by dialysis, taking tadalafil on a daily basis in patients with severe renal impairment is not recommended.

There are limited clinical data on the safety of a single dose of tadalafil in patients with severe hepatic impairment (Child-Pugh class C). Daily use of tadalafil for the treatment of erectile dysfunction and benign prostatic hyperplasia in patients with hepatic impairment has not been evaluated. Therefore, when prescribing tadalafil, a physician should conduct a thorough individual assessment of the ratio of benefits and risks of its use.

Priapism and anatomical deformity of the penis

Patients should be informed of the need for immediate medical attention in case of an erection lasting 4 hours or more. Late treatment of priapism leads to damage to the tissues of the penis, resulting in irreversible impotence.

Tadalafil should be used with caution in patients with anatomical deformity of the penis (angular curvature, cavernous fibrosis or disease Peyronie's) or in patients with a predisposition to priapism (with sickle cell anemia, multiple myeloma or leukemia).

Use of CYP3A4 inhibitors

Caution should be exercised when prescribing tadalafil to patients using CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, and erythromycin), since an increase in the AUC values ​​of tadalafil was observed with the combined use of these drugs.

Tadalafil and other erectile dysfunction treatments

The safety and efficacy of combinations of tadalafil and other PDE5 inhibitors or other erectile dysfunction treatments have not been studied. Patients should be informed that taking tadalafil in combination with these drugs is undesirable.

Lactose

The drug contains lactose. Patients with rare hereditary disorders of galactose tolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.

Interaction with other drugs

Drug interaction studies were performed with tadalafil 10 mg and / or 20 mg, as directed below. With regard to those interaction studies in which only the 10 mg dose of tadalafil was used, clinically significant interactions cannot be completely ruled out when using higher doses.

Effect of other drugs on tadalafil

Inhibitors of cytochrome P450

Tadalafil is mainly metabolized by the CYP3A4 isoenzyme. Selective inhibitor of the isoenzyme CYP3A4 ketoconazole at a dose of 200 mg per day increases the AUC of tadalafil (10 mg) by 2 times and the Cmax of tadalafil by 15% relative to the AUC and Cmax values ​​when using tadalafil in monotherapy. And ketoconazole at a dose of 400 mg per day increases the AUC of tadalafil (20 mg) by 4 times and the Cmax of tadalafil by 22%.

The protease inhibitor ritonavir (200 mg twice a day), which inhibits the activity of isoenzymes CYP3A4, CYP2C9, CYP2C19 and CYP2D6, increased the AUC of tadalafil (20 mg) by 2 times without changing Cmax. Although specific interactions with other protease inhibitors such as saquinavir and other CYP3A4 inhibitors such as erythromycin, clarithromycin, itraconazole, and grapefruit juice have not been studied, they should be coadministered with tadalafil with caution as they may increase plasma concentrations of tadalafil ... Consequently, the frequency of adverse reactions may increase.

Carriers

The role of transporters (eg, P-glycoprotein) in the distribution of tadalafil is unknown. There is the possibility of drug interactions mediated by inhibition of vectors.

Cytochrome P450 inducers

A selective inducer of the CYP3A4 isoenzyme, rifampicin, reduces the AUC value of tadalafil by 88% in comparison with the AUC values ​​with tadalafil monotherapy (10 mg). Perhaps this reduces the effectiveness of tadalafil; the extent to which efficiency is reduced is unknown. It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) can also reduce the concentration of tadalafil in the blood plasma.

Storage conditions

Store in a dark place at a temperature not exceeding +25 C.

Keep out of the reach of children.

Shelf life is 2 years.