Tadalafil is indicated for the treatment of erectile dysfunction in men. Sexual stimulation is required for this product
The main ingredients of this product are: Tadalafil
Molecular formula: C22H19N3O4
Molecular weight: 389.41
The 10mg tablets are light yellow, almond-shaped, and marked with "C10" on one side.
Treatment of male erectile dysfunction. Sexual stimulation is required for this product to take effect. Tadalafil cannot be used in women.
For adult males
The recommended dose of this product is 10mg, which is taken before sexual life and will not be affected by eating. If the effect of taking 10mg is not significant, you can take 20mg. It can be taken at least 30 minutes before sex.
The maximum frequency of medication is once a day.
It is best not to take tadalafil continuously every day, because the safety of long-term use has not been determined. At the same time, because the effect of tadalafil often lasts more than a day. (See the last paragraph of "Precautions" and "Pharmacology and Toxicology" for details)
For elderly men
The elderly do not need to adjust the dose.
For men with renal insufficiency
There is no need to adjust the dose for patients with mild to moderate renal insufficiency. For patients with severe renal insufficiency, the maximum recommended dose is 10 mg. (See "Pharmacokinetics" for details)
For men with liver insufficiency
The recommended dose of this product is 10mg, which is taken before sexual life and will not be affected by eating. There is limited information on the clinical safety of tadalafil in patients with severe hepatic insufficiency (Child-Pugh grade C); if such patients are prescribed, the prescribing doctor needs to conduct a careful benefit/risk assessment of each patient. There is no data on patients with hepatic insufficiency taking doses higher than 10 mg. ("Precautions" and "Pharmacokinetics")
For men with diabetes
There is no need to adjust the dose for diabetic patients.
Used in children and adolescents
Those under the age of 18 are not allowed to take this product.
The most commonly reported side effects are headaches and indigestion, as shown in the table below.
Clinical studies have shown that tadalafil can enhance the antihypertensive effect of nitrate drugs. This is believed to be the result of nitrate drugs and tadalafil acting together on the nitric oxide/cGMP pathway. Therefore, patients who are taking any form of nitrate drugs are prohibited from taking this product. (See "Drug Interactions" for details)
Sexual life can bring potential heart risks to patients with heart disease. Therefore, treatments for erectile dysfunction, including tadalafil, should not be used for heart patients who are advised not to have sex. For patients who already have heart disease, doctors should consider the potential heart risks of sex. The clinical trials that have been conducted do not include patients with the following cardiovascular diseases, so these populations are strictly prohibited from taking tadalafil:
Patients who have had myocardial infarction in the last 90 days
Patients with unstable angina or who have had angina during intercourse
Patients with heart failure who have met the diagnostic criteria of the New York Heart Association Grade 2 or above in the past 6 months
Patients with refractory arrhythmia, hypotension ([90/50mmHg), or refractory hypertension
Patients who have had a stroke in the last 6 months
Patients who are known to be allergic to tadalafil and the ingredients in its prescription should not take this product.
Before considering drug treatment, medical history and physical examination of the patient should be taken to diagnose whether there is male erectile dysfunction and to determine the possible unknown cause.
Because the incidence of cardiovascular disease is related to a certain degree of sexual behavior, doctors should consider the patient’s cardiovascular health before treating men with erectile dysfunction, including tadalafil. Because tadalafil has the property of making blood vessels dilate, it will cause a mild, short-term decrease in blood pressure (see "Pharmacology and Toxicology"), which may enhance the antihypertensive effect of nitrate (see "Contraindications").
Severe cardiovascular diseases, including myocardial infarction, unstable angina, ventricular arrhythmia, shock, transient ischemic attack, etc., have been observed in clinical trials of tadalafil. In addition, hypertension and hypotension (including orthostatic hypotension) can occasionally be seen in clinical trials. Most of the above-mentioned patients have cardiovascular disease factors before taking the medicine. However, it is not yet certain whether these events are related to these risk factors.
There is limited information on the clinical safety of this product in patients with severe hepatic insufficiency (Child-Pugh grade C); if such patients are prescribed, the prescribing doctor is required to conduct a careful benefit/risk assessment of each patient.
Clinical trials of tadalafil have not reported the occurrence of priapism. But sildenafil, another PDE5 inhibitor, has reported priapism. Patients should be informed that they must seek immediate treatment when they have an erection of more than 4 hours or longer. If the priapism is not treated in time, it may cause damage to the penile tissue and permanent loss of erection ability.
Tadalafil should be used with caution in the following patients: patients prone to priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or patients with abnormal penile anatomy (such as penile angulation, malformed penis, cavernous fibrosis) Or Peyronie disease).
The diagnosis of erectile dysfunction should include clarifying the underlying cause and determining the corresponding treatment after proper evaluation. As for whether this product is effective for patients with spinal cord injury, patients who have undergone pelvic surgery, and patients undergoing prostatectomy, it is still unclear.
Tadalafil cannot be used in the following patients: patients with genetic problems of galactose intolerance, or patients with galactose deficient, or patients with glucose-galactose malabsorption.
Patients who are using α1-receptor blockers, such as doxazosin, may cause symptomatic hypotension in some patients (see "Drug Interactions" for details). Therefore, it is not recommended to use tadalafil in combination with alpha-blockers.
If patients who are using powerful CYP3A4 inhibitors (such as ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin) are prescribed non-prescription tadala, special attention should be paid. Because tadalafil has been found to be used in combination with such drugs, it can increase tadalafil exposure (AUC) (see "Drug Interactions" for details)
The safety and efficacy of this product and other erectile dysfunction treatments have not been studied. Therefore, such combination is not recommended.
In a dog trial, tadalafil was administered at a dose of 25 mg/kg/day or more per day for 6 to 12 months (at least 3 times higher exposure than the single dose of 20 mg/day used in humans) Rate [range 3.7 to 18.6]), it was found that the vas deferens epithelial cells of some test dogs degenerated, which led to a decrease in sperm count. The results of a continuous 6-month study on healthy volunteers in the two groups showed that the clinical phenomenon observed in the dog test above does not occur in humans (see "Pharmacology and Toxicology"). The effect of long-term continuous daily use of tadalafil has not been determined, so continuous daily use is prohibited.
Tadalafil has no or negligible influence on the ability to drive and operate machinery. No special studies have been conducted on this potential impact. Although the frequency of vertigo reported in the placebo and tadalafil groups was similar in clinical trials, patients should still be aware of their reactions to tadalafil before driving or operating machinery.
Medication for pregnant and lactating women
This product is not for use in women. Tadalafil has not been studied in pregnant women. Rats and mice were given doses as high as 1000mg/kg/day, and there was no embryonic teratogenesis, embryotoxicity and fetal toxicity.
People under the age of 18 are not allowed to take this product.
The oral tadalafil clearance rate of healthy elderly subjects (65 years or older) is lower, making the AUC 25% higher than that of healthy subjects aged 19-45. The effect of this age has no clinical significance, and there is no need to adjust the dose.
10 mg and/or 20 mg tadalafil were used in the interaction studies described below. Since the dose used in the study is 10 mg tadalafil, when a larger dose is used clinically, clinically related drug interactions cannot be completely ruled out.
The effect of other drugs on tadalafil
Tadalafil is mainly metabolized by CYP3A4. Compared with the AUC value and Cmax of tadalafil alone, ketoconazole (200mg per day), a selective inhibitor of CYP3A4, can increase the exposure (AUC) of tadalafil (10mg) by 2 times and increase Cmax by 15 %. Ketoconazole (400mg per day) can increase the exposure (AUC) of tadalafil (20mg) by 4 times and increase Cmax by 22%. The protease inhibitor ritonavir (200mg, twice a day) is an inhibitor of CYP3A4, CYP2C9, CYP2C19 and CYP2D6, which can increase the exposure (AUC) of tadalafil (20mg) by 2 times, and has no effect on Cmax. Although no special interaction studies have been conducted, other protease inhibitors, such as saquinavir and other CYP3A4 inhibitors, such as erythromycin, erythromycin, itraconazole, and grapefruit juice, may increase tadal Concentration of Rafiel in plasma. Therefore, the incidence of unpredictable adverse reactions may increase.
The effect of "transport factors (such as P-glycoprotein) on the distribution of tadalafil is not clear." Therefore, drug interactions caused by inhibitors of transport factors may occur.
"Compared with the AUC value of tadalafil alone (10mg dose), the CYP3A4 inducer rifampicin can reduce the AUC of tadalafil to 88%. Based on this speculation, the combined application with other CYP3A4 inducers can also reduce the concentration of tadalafil in the plasma, such as: phenobarbital, phenytoin, and amidopyridine.
The effect of tadalafil on other drugs
Clinical studies have shown that tadalafil (10mg and 20mg) can enhance the antihypertensive effect of nitrate drugs. Therefore, patients who are taking any form of nitrate drugs are prohibited from taking this product (see "Contraindications"). Based on the results of a clinical study conducted in 150 subjects, 20 mg of tadalafil was administered at different times a day for 7 days and 0.4 mg of nitroglycerin sublingually. This interaction lasted more than 24 hours. There will be no interactions 48 hours after the last dose of tadalafil. Therefore, for patients taking tadalafil, the timing of nitrate administration should be determined based on the needs and conditions of the treatment, and nitrate administration should be considered at least 48 hours after the last dose of tadalafil. In this case, nitrate drugs can only be administered under strict medical monitoring and appropriate hemodynamic testing.
Tadalafil will not be eliminated by drugs metabolized by CYP450 isoforms and will produce clinically significant inhibition and induction. Studies have confirmed that tadalafil does not inhibit or induce CYP450 isoforms: CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
Tadalafil (10mg and 20mg) has no clinically significant effect on the distribution (AUC) of S-warfarin or R-warfarin (the substrate of CYP2C9); tadalafil induces warfarin The change of prothrombin time has no effect.
Tadalafil (10 mg and 20 mg) does not enhance the prolonged bleeding time caused by acetylsalicylic acid.
Clinical pharmacology studies have verified the potential of tadalafil to enhance the antihypertensive effect of antihypertensive drugs. The main types of antihypertensive drugs have been studied, including calcium channel blockers (amlodipine), angiotensin transferase (ACE) inhibitors (enalapril), β-adrenergic receptor antagonists (US Torol), thiazide diuretics (benzylfluorothiazide), angiotensin II receptor inhibitors (different types and doses, alone or with thiazides, calcium channel blockers, β-receptor antagonists, And/or alpha receptor inhibitors). Tadalafil (the study dose of angiotensin II receptor inhibitor is 10 mg, and the study dose of amlodipine is 20 mg) has no clinically significant interaction with any of the above drugs. In another clinical pharmacology study, the combined use of tadalafil (20mg) and four types of antihypertensive drugs was studied. In subjects who used multiple antihypertensive drugs, changes in blood pressure after exercise showed a correlation with the degree of blood pressure control. In this regard, the participants in the study whose blood pressure was well controlled had a small drop in blood pressure, which was similar to that of healthy subjects. In subjects whose blood pressure was not controlled, the blood pressure dropped significantly, although this decline was not related to symptoms of hypotension in most subjects. Generally speaking, in patients taking antihypertensive drugs at the same time, tadalafil 20mg promotes blood pressure drop (except for alpha blockers-see below -) is of little or impossible clinical relevance. The analysis of information from the phase III clinical study showed that patients who were given tadalafil with or without antihypertensive drugs had no difference in terms of adverse events. However, patients who are taking antihypertensive drugs should be informed that the combined use has the possibility of lowering blood pressure.
Alcohol concentration (average maximum blood concentration 0.08%) is not affected by taking tadalafil (10mg or 20mg) at the same time. There was no change in the concentration of tadalafil after taking it with alcohol for 3 hours. There was no change in the concentration of tadalafil after taking it with alcohol for 3 hours. Alcohol was given at the maximum alcohol absorption rate (fasting the night before until 2 hours after alcohol was given). Tadalafil (20mg) did not appear to be given a dose of alcohol (0.7g/kg or 40% alcohol (vodka)). An 80kg male (approximately 180ml) induced an increase in the decrease in mean blood pressure. However, orthostatic vertigo and orthostatic hypotension were observed in some subjects. However, when tadalafil was used in combination with low-dose alcohol (0.6g/kg), hypotension was not observed, and the frequency of dizziness was similar to that of alcohol alone. The effect of alcohol on cognitive function is not increased by the combined use of tadalafil (10mg).
Tadalafil has been proven to increase the bioavailability of ethinyl estradiol after oral administration. It can be speculated that tadalafil can also increase the bioavailability of orally administered terbutanine, but this clinical effect is currently unclear.
In clinical pharmacology trials, tadalafil (10mg) was used together with theophylline (a non-selective phosphodiesterase inhibitor), and no pharmacokinetic interaction was found. The only pharmacokinetic effect is a slight increase in heart rate (3.5 beats/min). Although this effect is small and has no significant significance in this clinical trial, it should still be considered when used in combination. The study on the interaction of tadalafil and hypoglycemic drugs in combination has not been conducted yet.
In healthy subjects, a single dose is as high as 500 mg, and the total dose of the patient's multiple daily doses has reached 100 mg. The adverse events are similar to those at lower doses. If an overdose occurs, standard supportive treatment should be used. Hemodialysis does not help much in the removal of tadalafil.
Pharmacology and Toxicology
Medication group: medication for erectile dysfunction (ATC code G04BE).
Tadalafil is a selective and reversible inhibitor of cyclic guanosine phosphate (cGMP) specific phosphodiesterase 5 (PDE5)