Tadalafil

Inside
Erectile disfunction. For patients with frequent sexual activity (more than 2 times / week): the recommended frequency of administration is daily, 1 time per day, 5 mg, at the same time, regardless of the meal. The daily dose can be reduced to 2.5 mg (1/2 tab. 5 mg), depending on the individual sensitivity. For patients with infrequent sexual activity (less often 2 times / week): the prescription of the drug Tadalafil-SZ in a dose of 20 mg is recommended, immediately before sexual activity as described. The maximum daily dose of the drug Tadalafil-SZ is 20 mg.
BPH or erectile dysfunction / BPH. The recommended dose of the drug Tadalafil-SZ when applied once a day is 5 mg; the drug should be taken at approximately the same time of the day, regardless of the time of sexual activity. The duration of treatment is determined by the doctor individually.
Renal failure. In patients with mild renal failure (Cl creatinine from 51 to 80 ml / min) and moderate severity (Cl creatinine from 31 to 50 ml / min), dose adjustment is not required. In patients with severe renal failure (Cl creatinine <30 ml="" min="" and="" on="" hemodialysis="" the="" use="" of="" drug="" tadalafil-sz="" is="" contraindicated="" br="">

Adverse reactions

The most frequent adverse events in patients with erectile dysfunction and BPH are headache and dyspepsia, as well as back pain, myalgia.
In accordance with the WHO classification, all reactions are distributed according to the system of organs and the frequency of development: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 \ 10000, <1 1000="" very="" rarely="" 1="" 10000="" frequency="" is="" unknown="" it="" impossible="" to="" determine="" the="" of="" occurrence="" reactions="" on="" basis="" available="" data="" br=""> On the part of the immune system: infrequently - hypersensitivity reactions; rarely, angioedema.
On the part of the nervous system: often - headache; infrequently - dizziness; seldom - stroke2 (including acute cerebral circulation (hemorrhagic) by hemorrhagic type), syncope, transient ischemic attacks2, migraine1, seizures1, transient amnesia.
On the part of the organ of vision: infrequently - blurred vision, pain in the eyeball; rarely - visual disturbances, eyelid swelling, conjunctival hyperemia, NAPION1, retinal vascular occlusion1.
On the part of the organ of hearing and labyrinth disorders: infrequently - ringing in the ears; rarely, sudden hearing loss.
From the side of the heart2: infrequently - palpitations, tachycardia; rarely, myocardial infarction, ventricular arrhythmias, unstable stenocardia1.
On the part of the vessels: often - flushing of the face; infrequently - decrease in blood pressure, increase in blood pressure.
On the part of the respiratory system, organs of the chest and mediastinum: often - nasal congestion; infrequently - shortness of breath, epistaxis.
On the part of the digestive tract: often - dyspepsia; infrequently - abdominal pain, gastroesophageal reflux, diarrhea in patients over 65, vomiting, nausea.
On the part of the skin and subcutaneous tissues: infrequently - rash; rarely - urticaria, Stevens-Johnson syndrome1, exfoliative dermatitis1, hyperhidrosis (excessive sweating).
On the part of the musculoskeletal system and connective tissue: often - back pain, myalgia, pain in the limbs.
On the part of the kidneys and urinary tract: infrequently - hematuria.
On the part of the genital organs and mammary gland: infrequently - prolonged erection; rarely - priapism, hematospermia, bleeding from the penis.
General disorders: infrequently - chest pain2, peripheral edema, fatigue; rarely - swelling of the face1, sudden cardiac death1, 2.

1. Adverse reactions identified during post-marketing use, not observed during clinical placebo-controlled studies.
2. Observed in patients who previously had cardiovascular risk factors.However, it is not possible to determine whether these phenomena are directly related to these risk factors, tadalafil, sexual arousal, or a combination of these or other factors.
3. More often observed when tadalafil was used in patients already taking antihypertensive drugs.

Contraindications

• Hypersensitivity to tadalafil or any substance that is part of the drug;
• taking drugs containing any organic nitrates;
• 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 occurrence of angina during sexual intercourse, chronic heart failure II class and higher according to the NYHA classification for the last 6 months, uncontrolled arrhythmias, arterial hypotension (BP <90/50 mmHg), uncontrolled arterial hypertension, ischemic stroke during the last 6 months;
• loss of vision due to non-arterial anterior ischemic optic neuropathy (NAPION) (regardless of the connection with the intake of PDE-5 inhibitors);
• simultaneous use with doxazosin, other PDE-5 inhibitors, other erectile dysfunction therapies, and guanylate cyclase stimulants, such as riociguat;
• chronic renal failure (Cl creatinine <30 ml="" min="" li="">
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• age up to 18 years.

With caution: severe hepatic impairment (Child-Pugh class C) (there is not enough data for these patients); simultaneous administration of alpha1-adrenergic blockers (simultaneous use of these drugs can lead to symptomatic arterial hypotension in some patients; when a single dose of tadalafil is used, symptomatic arterial hypotension is not observed with simultaneous use with tamsulosin, a selective alpha1A-adrenergic blocker (see "Interaction"); predisposition to priapism (with sickle cell anemia, multiple myeloma, or leukemia) or anatomical deformation of the penis (angular curvature , cavernous fibrosis or Peyronie's disease); simultaneous use with CYP3A4 ioenzyme inhibitors ip (including ritonavir, saquinavir, ketoconazole, itraconazole, clarithromycin, erythromycin, grapefruit juice), hypotensive agents, 5-inhibitors, 5-inhibitors, 5-inhibitors, 5-inhibitors, 5-inhibitors, ip-5, syrup, syrup, glidromycin, erythroconazole, erythromycinum, erythroconazole, clarification of the antihypertensive drug
Diagnosing erectile dysfunction should include identifying a potential underlying cause, appropriate medical examination, and determining treatment tactics.

Drug interactions

Effect of other drugs on tadalafil
Tadalafil is mainly metabolized with the participation of CYP3A4 isoenzyme. The selective CYP3A4 isoenzyme inhibitor ketoconazole (400 mg / day) increases the exposure of a single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketoconazole (200 mg / day) increases the exposure of a single dose of tadalafil (AUC) to 107% and Cmax 15% relative to AUC and Cmax values ​​for tadalafil only.
Ritonavir (200 mg 2 times a day), an inhibitor of isoenzymes CYP3A4, CYP2С9, CYP2С19 and CYP2D6, increases the 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 saquinavir, as well as CYP3A4 isoenzyme inhibitors, such as erythromycin, clarithromycin, itraconazole, and grapefruit juice, can increase plasma levels of tadalafil. The role of carriers (including P-gp) in the distribution of tadalafil is unknown. There is the possibility of drug interaction mediated by vector inhibition.
Selective inducer of CYP3A4 isoenzyme, rifampicin (at a dose of 600 mg / day), reduces the exposure of a single dose of tadalafil (AUC) by 88% and Cmax by 46% relative to AUC and Cmax for only tadalafil.It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) should also reduce plasma plasma tadalafil concentrations.
The simultaneous taking of an antacid (magnesium hydroxide / aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the AUC for tadalafil.
An increase in the pH of the stomach as a result of taking the H2-histamine receptor blocker nizatidine did not affect the pharmacokinetics of tadalafil.
The safety and efficacy of tadalafil combination with other types of treatment of erectile dysfunction or other PDE-5 inhibitors have not been studied, so the use of such combinations is not recommended.
The effect of tadalafil on other drugs
It is known that tadalafil enhances 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) and cGMP. Therefore, the use of tadalafil on the background of taking nitrates is contraindicated.
Tadalafil has no clinically significant effect on the clearance of drugs whose metabolism proceeds with the participation of cytochrome P450.
Studies have confirmed that tadalafil does not inhibit and does not induce CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP2E1 isoenzymes.
Tadalafil has no clinically significant effect on the AUC of S- or R-warfarin. Tadalafil does not affect the effect of warfarin on PV.
Tadalafil does not potentiate the increase in the duration of bleeding caused by the administration of acetylsalicylic acid.
Tadalafil has systemic vasodilating properties and may enhance the action of antihypertensive drugs. Additionally, in patients taking several antihypertensive drugs, in which arterial hypertension was poorly controlled, there was a slightly greater decrease in blood pressure. In the vast majority of patients, this reduction was not associated with hypotensive symptoms. Patients receiving antihypertensive drugs and receiving tadalafil should be given appropriate clinical guidelines.
No significant decrease in blood pressure was observed with simultaneous use of tadalafil and selective tamsulosin alpha1A-blocker by healthy volunteers.
The simultaneous use of tadalafil with doxazosin is contraindicated. When tadalafil was used by healthy volunteers who took doxazosin (4–8 mg / day), alpha1-blocker, there was an increase in the doxazosin hypotensive effect. Some patients experienced symptoms associated with a decrease in blood pressure, including syncope.
Simultaneous administration of riociguat with PDE-5 inhibitors, including tadalafil, is contraindicated because riociguat enhances the hypotensive effect of PDE-5 inhibitors.
Studies of drug interactions of tadalafil and 5-alpha reductase inhibitors have not been carried out, with their simultaneous use caution should be exercised.
Tadalafil causes an increase in the bioavailability of ethinyl estradiol when taken orally. A similar increase in bioavailability can be expected when taking terbutaline, but the clinical effects have not been established.
Tadalafil did not affect the concentration of alcohol, nor did alcohol affect the concentration of tadalafil. With high doses of alcohol (0.7 g / kg), tadalafil intake did not cause a statistically significant decrease in the mean BP. Some patients had postural dizziness and orthostatic hypotension. 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 has no clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.

Special instructions

Overdosage