Drug Name

Tadalis SX (Tadalafil)

Pharmacological action

A remedy for erectile dysfunction, it is a reversible selective inhibitor of specific FDE5 cGMF. When sexual arousal causes local release of nitric oxide, inhibition of FDE5 by tadalafil leads to increase of cGMP level in the corpora cavernosa of the penis. The consequence of this is relaxation of arterial smooth muscles and blood flow to the tissues of the penis, which causes an erection. Tadalis SX (Tadalafil) is ineffective in the absence of sexual stimulation.

In vitro studies have shown that tadalafil is a selective inhibitor of FDE5. FDE5 is an enzyme found in the smooth muscles of the cavernous body, in the smooth muscles of vessels of internal organs, in skeletal muscles, platelets, kidneys, lungs, cerebellum.

The action of Tadalis SX (Tadalafil) on FDE5 is more active than on other phosphodiesterases. Tadalis SX (Tadalafil) is 10,000 times more active against FDE5 than against FDE1, FDE2, FDE4, which are localized in the heart, brain, blood vessels, liver, and other organs. Tadalis SX (Tadalafil) is 10,000 times more active in blocking FDE5 than FDE3, an enzyme found in the heart and blood vessels. This selectivity for FDE5, compared to FDE3, is important because FDE3 is an enzyme involved in heart muscle contraction. In addition, tadalafil is about 700 times more active against FDEF5 than against FDEF6, which is found in the retina and is responsible for phototransmission. Tadalis SX (Tadalafil) is also 10,000 times more active against FDE5 compared to its effect on FDE7-FDE10.

Its effect lasts for 36 hours. The effect appears as early as 16 minutes after oral administration in the presence of sexual arousal.

Tadalis SX (Tadalafil) in healthy subjects causes no significant changes in systolic and diastolic blood pressure compared to placebo when lying down (mean maximum decrease is 1.6/0.8 mm Hg, respectively) and when standing (mean maximum decrease is 0.2/4.6 mm Hg, respectively). Tadalafil causes no significant change in HR.

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

No clinically significant effect on the characteristics of sperm in men who took tadalafil in daily doses for 6 months was found.

Pharmacokinetics

After oral administration, tadalafil is rapidly absorbed. Cmax is reached on average in 2 hours. The speed and degree of absorption are not dependent on food intake. The pharmacokinetics of tadalafil in healthy individuals are linear with respect to time and dose. In the dose range from 2.5 to 20 mg, the AUC increases in proportion to the dose. Plasma Css are reached within 5 days when the drug is taken once daily.

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

The Vd is about 63 L, indicating that tadalafil is distributed in body tissues. At therapeutic concentrations, 94% of tadalafil is bound to plasma proteins. In healthy individuals, less than 0.0005% of the administered dose is found in semen.

It is metabolized with participation of CYP3A4 isoenzyme. The major circulating metabolite is methylcatecholglucuronide, which is 13,000 times less active against FDE5 than tadalafil, so it is unlikely that this metabolite is clinically significant.

In healthy individuals, the average clearance of tadalafil when taken orally is 2.5 L/h, and the average T1/2 is 17.5 h. Tadalafil is excreted mainly as inactive metabolites, mainly in the faeces (about 61%) and to a lesser extent in the urine (about 36%).

In patients with mild (CKR 51 to 80 ml/min) or moderate (CKR 31 to 50 ml/min) renal insufficiency, the AUC is greater than in healthy subjects.

Contraindications to use

Simultaneous use of drugs containing any organic nitrates; children and adolescents under 18 years of age; hypersensitivity to tadalafil.

Usage during pregnancy and lactation

The drug is not used in women.

Application in liver dysfunction

With special caution and only in case of extreme necessity, tadalafil can be used in patients with severe hepatic insufficiency.

Use in patients with impaired renal function

With special caution and only in case of extreme necessity tadalfil can be used in patients with severe renal insufficiency (CK≤30 ml/min).

During tadalfil treatment, patients with moderate renal insufficiency (CKD of 31 to 50 ml/min) more often had back pain compared to patients with mild renal insufficiency (CKD of 51 to 80 ml/min) or healthy volunteers. In patients with CK≤50 ml/min, tadalphil should be used with caution

Use in children

Contraindicated in children and adolescents under 18 years of age.

Indications of the active substances of the drug Tadalis SX (Tadalafil)

Erectile dysfunction.

Dosing regimen

In middle-aged men, it is recommended that a dose of 20 mg be taken at least 16 min before intended sexual activity, regardless of food intake. Patients may attempt sexual intercourse at any time within 36 h after ingestion in order to establish optimal response time to tadalafil administration. The maximum frequency of administration is once daily.