Tadalear^® (Tablets) Instructions for Use

Marketing Authorization Holder

Rapharma, JSC (Russia)

ATC Code

G04BE08 (Tadalafil)

Active Substance

Tadalafil (Rec.INN registered by WHO)

Dosage Form

Tadalear®

Film-coated tablets, 20 mg

Dosage Form, Packaging, and Composition

Film-coated tablets

10 pcs. – blister packs (3 pcs.) – cardboard packs (30 pcs.) – By prescription
10 pcs. – blister packs (6 pcs.) – cardboard packs (60 pcs.) – By prescription
14 pcs. – blister packs (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blister packs (4 pcs.) – cardboard packs (56 pcs.) – By prescription

Clinical-Pharmacological Group

Erectile dysfunction treatment drug. PDE5 inhibitor

Pharmacotherapeutic Group

Drugs used in urology; drugs for the treatment of erectile dysfunction

Pharmacological Action

A drug for the treatment of erectile dysfunction, it is a reversible selective inhibitor of specific cGMP PDE5. When sexual stimulation causes local release of nitric oxide, inhibition of PDE5 by tadalafil leads to an increase in cGMP levels in the corpus cavernosum of the penis.

The consequence of this is relaxation of the smooth muscles of the arteries and blood flow to the tissues of the penis, which causes an erection. Tadalafil is not effective in the absence of sexual stimulation.

In vitro studies have shown that Tadalafil is a selective inhibitor of PDE5. PDE5 is an enzyme found in the smooth muscles of the corpus cavernosum, in the smooth muscles of visceral vessels, in skeletal muscles, platelets, kidneys, lungs, and cerebellum.

The effect of tadalafil on PDE5 is more potent than on other phosphodiesterases. Tadalafil is 10,000 times more potent against PDE5 than against PDE1, PDE2, PDE4, which are localized in the heart, brain, blood vessels, liver, and other organs.

Tadalafil blocks PDE5 10,000 times more potently than PDE3, an enzyme found in the heart and blood vessels. This selectivity for PDE5, compared to PDE3, is important because PDE3 is an enzyme involved in myocardial contraction.

Furthermore, Tadalafil is approximately 700 times more potent against PDE5 than against PDE6, found in the retina and responsible for phototransduction. Tadalafil is also 10,000 times more potent against PDE5 compared to its effect on PDE7-PDE10.

It acts for 36 hours. The effect appears as early as 16 minutes after oral administration in the presence of sexual stimulation.

In healthy individuals, Tadalafil does not cause a significant change in systolic and diastolic blood pressure compared to placebo in the supine position (mean maximum decrease is 1.6/0.8 mmHg, respectively) and standing (mean maximum decrease is 0.2/4.6 mmHg, respectively). Tadalafil does not cause a significant change in heart rate.

Tadalafil does not cause changes in color discrimination (blue/green), which is explained by its low affinity for PDE6. Furthermore, no effect of tadalafil on visual acuity, electroretinogram, intraocular pressure, or pupil size was noted.

No clinically significant effect on sperm characteristics was found in men taking Tadalafil in daily doses for 6 months.

Pharmacokinetics

After oral administration, Tadalafil is rapidly absorbed. C_max is reached on average in 2 hours. The rate and extent of absorption do not depend 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, AUC increases proportionally to the dose. C_ss in plasma is reached within 5 days when taking the drug once a day.

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

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

It is metabolized with the participation of the CYP3A4 isoenzyme. The main circulating metabolite is methylcatechol glucuronide, which is 13,000 times less active against PDE5 than Tadalafil, so it is unlikely that this metabolite is clinically significant.

In healthy individuals, the average clearance of tadalafil after oral administration is 2.5 L/h, and the average T_1/2 is 17.5 hours. Tadalafil is excreted predominantly as inactive metabolites, mainly in feces (about 61%) and to a lesser extent in urine (about 36%).

In patients with mild renal impairment (creatinine clearance from 51 to 80 ml/min) or moderate renal impairment (creatinine clearance from 31 to 50 ml/min), AUC is higher than in healthy individuals.

Indications

Erectile dysfunction.

ICD codes

Dosage Regimen

Take one 20 mg tablet orally at least 16 minutes before anticipated sexual activity.

Administer the dose once daily as the maximum frequency.

Ingest the tablet with or without food; food intake does not affect absorption.

The therapeutic effect and the ability to achieve an erection with sexual stimulation can persist for up to 36 hours after a single dose.

Determine the individual optimal response time within this 36-hour window.

For patients with severe renal impairment (creatinine clearance ≤30 mL/min), use a maximum dose of 10 mg once daily and exercise caution.

In patients with severe hepatic impairment (Child-Pugh Class C), restrict the maximum dose to 10 mg and use with caution.

Avoid concomitant use with any form of organic nitrates due to the risk of severe hypotension.

Do not use Tadalafil in combination with any other treatments for erectile dysfunction.

Adverse Reactions

Most frequently headache, dyspepsia.

Possibly back pain, myalgia, nasal congestion, facial flushing.

Rarely eyelid edema, eye pain, conjunctival hyperemia, dizziness.

Contraindications

Concomitant use of drugs containing any organic nitrates; childhood and adolescence under 18 years of age; hypersensitivity to tadalafil.

Use in Pregnancy and Lactation

The drug is not used in women.

Use in Hepatic Impairment

With particular caution and only in case of extreme necessity, the use of tadalafil in patients with severe hepatic impairment is possible.

Use in Renal Impairment

With particular caution and only in case of extreme necessity, the use of tadalafil in patients with severe renal impairment (creatinine clearance ≤30 ml/min) is possible.

During treatment with tadalafil, back pain was more frequently noted in patients with moderate renal impairment (creatinine clearance from 31 to 50 ml/min) compared to patients with mild renal impairment (creatinine clearance from 51 to 80 ml/min) or healthy volunteers. In patients with creatinine clearance ≤50 ml/min, tadalafil should be used with caution.

Pediatric Use

Contraindicated in childhood and adolescence under 18 years of age.

Special Precautions

With particular caution and only in case of extreme necessity, the use of tadalafil in patients with severe renal impairment (creatinine clearance ≤30 ml/min) and severe hepatic impairment is possible.

During treatment with tadalafil, back pain was more frequently noted in patients with moderate renal impairment (creatinine clearance from 31 to 50 ml/min) compared to patients with mild renal impairment (creatinine clearance from 51 to 80 ml/min) or healthy volunteers. In patients with creatinine clearance ≤50 ml/min, Tadalafil should be used with caution.

Therefore, treatment of erectile dysfunction, including with the use of tadalafil, should not be carried out in men with such heart diseases where sexual activity is not recommended.

The potential risk of complications during sexual activity in patients with cardiovascular diseases should be considered: myocardial infarction within the last 90 days; unstable angina or angina occurring during sexual intercourse; chronic heart failure (functional class II and higher according to the NYHA classification) that developed within the last 6 months; uncontrolled cardiac arrhythmias; arterial hypotension (BP less than 90/50 mmHg) or uncontrolled arterial hypertension; stroke within the last 6 months.

Tadalafil should be used with caution in patients predisposed to priapism (for example, with sickle cell anemia, multiple myeloma, or leukemia) or in patients with anatomical deformation of the penis (for example, angulation, cavernous fibrosis, or Peyronie’s disease).

The patient should be informed of the need to immediately consult a doctor in case of an erection lasting 4 hours or more. Untimely treatment of priapism leads to damage to the tissues of the penis, as a result of which long-term loss of potency may occur.

No cases of priapism were reported during the use of tadalafil.

It is not recommended to use Tadalafil in combination with other types of treatment for erectile dysfunction.

Drug Interactions

Tadalafil is mainly metabolized with the participation of the CYP3A4 enzyme. The selective CYP3A4 inhibitor ketoconazole increases AUC by 107%, and rifampicin reduces it by 88%.

Although specific interactions have not been studied, it can be assumed that protease inhibitors such as ritonavir and saquinavir, as well as CYP3A4 inhibitors such as erythromycin and itraconazole, increase the activity of tadalafil.

When taking an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil simultaneously, the absorption rate of the latter decreases without changing its AUC.

Tadalafil enhances the hypotensive effect of nitrates. This occurs as a result of the additive action of nitrates and tadalafil on the metabolism of nitric oxide and cGMP. Therefore, the use of tadalafil in patients receiving nitrates is contraindicated.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.