Tadalafil-SZ, 5 mg 30 pcs
€15.46 €12.88
Pharmacodynamics
Tadalafil is a reversible selective inhibitor of specific phosphodiesterase type 5 (FDE-5) cyclic guanosine monophosphate (cGMP). When sexual arousal causes local release of nitric oxide, inhibition of FDE-5 by tadalafil leads to increased concentration of cGMP in the cavernous body 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. Tadalafil has no effect in the absence of sexual arousal.
In vitro studies have shown that tadalafil is a selective inhibitor of FDE-5. FDE-5 is an enzyme found in the smooth muscles of the cavernous body, in vascular smooth muscles of internal organs, in skeletal muscles, platelets, kidneys, lungs and cerebellum.
The action of tadalafil on FDE-5 is more active than on other phosphodiesterases. Tadalafil is 10,000 times more potent against FDE-5 than against FDE-1, FDE-2, FDE-4 and FDE-7, which are localized in the heart, brain, blood vessels, liver, white blood cells, skeletal muscles and other organs.
Tadalafil is 10,000 times more active in blocking FDE-5 than FDE-3, an enzyme found in the heart and blood vessels. This selectivity for FDE-5 over FDE-3 is important because FDE-3 is an enzyme involved in heart muscle contraction. In addition, tadalafil is about 700 times more active against FDE-5 than against FDE-6, which is found in the retina and is responsible for phototransmission.
Tadalafil is also 9,000 times more potent against FDE-5 compared to its effect on FDE-8, FDE-9 and FDE-10, and 14 times more potent against FDE-5 compared to FDE-11. Distribution in tissues and physiological effects of FDE-8 to FDE-11 inhibition have not yet been elucidated. Tadalafil improves erection and increases the possibility of a full sexual intercourse.
Tadalafil in healthy subjects causes no significant change in systolic and diastolic blood pressure compared to placebo in the supine position (mean maximum decrease is 1.6/0.8 mm Hg, respectively) and in the standing position (mean maximum decrease is 0.2/4.6 mm Hg, respectively).
Tadalafil causes no significant change in heart rate. Tadalafil does not cause changes in color recognition (blue/green), which is due to its low affinity for FDE-6. In addition, there is no effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size.
To evaluate the effect of daily tadalafil administration on spermatogenesis, several studies have been conducted. No undesirable effect on sperm morphology and motility was observed in any of the studies.
One study found a decrease in average sperm concentration compared to placebo. The decrease in sperm concentration was associated with a higher frequency of ejaculation. In addition, there was no undesirable effect on the average concentration of sex hormones, testosterone, luteinizing hormone and follicle stimulating hormone when taking tadalafil compared to placebo.
An improvement in erections in patients with erectile dysfunction of all degrees of severity when tadalafil is taken once daily has been observed.
Mechanism of action in patients with benign prostatic hyperplasia (BPH)
Inhibition of FDE-5 by tadalafil, resulting in increase of cGMP concentration in cavernous body of penis, is also observed in smooth muscles of prostate, bladder and blood vessels which supply them.
The relaxation of vascular smooth muscles leads to increased blood perfusion in these organs and, as a consequence, to a reduction in the severity of BPH symptoms. Relaxation of the smooth muscles of the prostate and bladder may additionally enhance vascular effects.
Pharmacokinetics
Intake
After oral administration, tadalafil is rapidly absorbed. Mean maximum plasma concentrations (Stah) are reached on average 2 hours after oral administration.
The speed and degree of absorption of tadalafil are not dependent on food intake, so Tadalafil-SZ can be used regardless of food intake. The time of intake (morning or evening) has no effect on the speed and degree of absorption.
The pharmacokinetics of tadalafil in healthy subjects are linear with respect to time and dose. In the dose range of 2.5 to 20 mg, the area under the concentration-time curve (AUC) increases in proportion to the dose. Equilibrium plasma concentrations are reached within 5 days if the drug is taken once daily.
The pharmacokinetics of tadalafil in patients with erectile dysfunction is similar to the pharmacokinetics of the drug in patients without erectile dysfunction.
Distribution
The average volume of distribution is about 63 liters, indicating that tadalafil is distributed in body tissues. In therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins. Protein binding is not altered in impaired renal function.
In healthy volunteers, less than 0.0005% of the administered dose is detected in semen.
Metabolism
Tadalafil is mainly metabolized with participation of cytochrome P450 isoenzyme CYP3A4. The main circulating metabolite is methylcatecholglucuronide. This metabolite is at least 13,000 times less active against FDE-5 than tadalafil. Consequently, the concentration of this metabolite is not clinically significant.
In healthy volunteers, the average clearance of tadalafil when taken orally is 2.5 l/h and the average half-life is 17.5 hours. Tadalafil is excreted mainly as inactive metabolites, mainly through the intestine (about 61% of the dose) and, to a lesser extent, by the kidneys (about 36% of the dose).
Particular Patient Groups
Age > 65 years
Healthy volunteers aged 65 years and older had lower clearance of tadalafil when ingested, as evidenced by a 25% increase in the area under the “concentration-time” curve compared to healthy volunteers aged 19 to 45 years. This difference is not clinically significant and does not require dose adjustment.
Renal Impairment
. In patients with mild renal failure (creatinine clearance of 51 to 80 ml/min) and moderate renal failure (creatinine clearance of 31 to 50 ml/min), as well as in patients with end-stage renal failure on hemodialysis, tadalafil exposure (AUC) approximately doubled.
The AUC was 41% higher in patients on hemodialysis compared to healthy volunteers. Excretion of tadalafil by hemodialysis is insignificant.
Hepatic impairment
The pharmacokinetics of tadalafil in patients with mild to moderate hepatic impairment (Child-Pugh class A and B) are comparable to those in healthy volunteers. There are insufficient data in patients with severe hepatic impairment (Child-Pugh class C). When prescribing Tadalafil-SZ in patients with severe hepatic impairment, a prior risk-benefit assessment should be performed.
Patients with Diabetes Mellitus
Patients with diabetes mellitus on tadalafil had approximately 19% less area under the concentration-time curve compared to healthy volunteers. This difference does not require a dose adjustment.
Indications
Erectile dysfunction;
lower urinary tract symptoms in patients with benign prostatic hyperplasia (for a dosage of 5 mg);
erectile dysfunction in patients with lower urinary tract symptoms due to benign prostatic hyperplasia (for a dosage of 5 mg).
Pharmacological effect
Pharmacodynamics
Tadalafil is a reversible selective inhibitor of specific phosphodiesterase type 5 (PDE-5) of cyclic guanosine monophosphate (cGMP). When sexual arousal causes local release of nitric oxide, inhibition of PDE5 by tadalafil leads to increased concentrations of cGMP in the corpus cavernosum of the penis. The consequence of this is the relaxation of the smooth muscles of the arteries and the flow of blood to the tissues of the penis, which causes an erection. Tadalafil has no effect in the absence of sexual arousal.
In vitro studies have shown that tadalafil is a selective PDE5 inhibitor. PDE-5 is an enzyme found in the smooth muscle of the corpus cavernosum, vascular smooth muscle of the internal organs, skeletal muscle, platelets, kidneys, lungs and cerebellum.
The effect of tadalafil on PDE-5 is more active than on other phosphodiesterases. Tadalafil is 10,000 times more potent against PDE-5 than against PDE-1, PDE-2, PDE-4 and PDE-7, which are localized in the heart, brain, blood vessels, liver, white blood cells, skeletal muscles and other organs.
Tadalafil is 10,000 times more potent at blocking PDE-5 than PDE-3, an enzyme found in the heart and blood vessels. This selectivity for PDE-5 over PDE-3 is important because PDE-3 is an enzyme involved in cardiac muscle contraction. In addition, tadalafil is approximately 700 times more active against PDE-5 than against PDE-6, which is found in the retina and is responsible for phototransmission.
Tadalafil is also 9000 times more potent against PDE5 than it is against PDE8, PDE9 and PDE10, and 14 times more potent against PDE5 than it is against PDE11. The tissue distribution and physiological effects of PDE-8 – PDE-11 inhibition have not yet been clarified. Tadalafil improves erection and increases the possibility of full sexual intercourse.
Tadalafil in healthy individuals does not cause significant changes in systolic and diastolic blood pressure compared to placebo in the supine position (average maximum decrease is 1.6/0.8 mmHg, respectively) and in the standing position (average maximum decrease is 0.2/4.6 mmHg, respectively).
Tadalafil does not significantly change heart rate. Tadalafil does not cause changes in color recognition (blue/green), which is explained by its low affinity for PDE-6. In addition, there was no effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size.
Several studies have been conducted to evaluate the effect of daily tadalafil on spermatogenesis. No adverse effects on sperm morphology or motility were observed in any of the studies.
One study found a decrease in mean sperm concentration compared to placebo. Decreased sperm concentration was associated with higher ejaculation frequency. In addition, no adverse effects were observed on mean concentrations of the sex hormones testosterone, luteinizing hormone, and follicle-stimulating hormone with tadalafil compared to placebo.
An improvement in erection was noted in patients with erectile dysfunction of all degrees of severity when taking tadalafil once a day.
Mechanism of action in patients with benign prostatic hyperplasia (BPH)
Inhibition of PDE5 by tadalafil, leading to increased concentrations of cGMP in the corpus cavernosum of the penis, is also observed in the smooth muscles of the prostate, bladder and the vessels that supply them.
Relaxation of vascular smooth muscle leads to an increase in blood perfusion in these organs, and, as a result, to a decrease in the severity of BPH symptoms. Relaxation of prostate and bladder smooth muscle may further enhance the vascular effects.
Pharmacokinetics
Suction
After oral administration, tadalafil is rapidly absorbed. The average maximum concentration (Cmax) in plasma is reached on average 2 hours after ingestion.
The rate and extent of absorption of tadalafil do not depend on food intake, so Tadalafil-SZ can be used regardless of food intake. The time of administration (morning or evening) does not affect the speed and extent of absorption.
The pharmacokinetics of tadalafil in healthy individuals is linear with respect to time and dose. In the dose range from 2.5 to 20 mg, the area under the concentration-time curve (AUC) increases proportionally to the dose. Equilibrium plasma concentrations are achieved 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 patients without erectile dysfunction.
Distribution
The average volume of distribution is approximately 63 L, which indicates that tadalafil is distributed into the tissues of the body. At therapeutic concentrations, 94% of tadalafil in plasma is protein bound. Protein binding is not affected by impaired renal function.
In healthy volunteers, less than 0.0005% of the administered dose was found in semen.
Metabolism
Tadalafil is mainly metabolized with the participation of the cytochrome P450 isoenzyme CYP3A4. The main circulating metabolite is methylcatechol glucuronide. This metabolite is at least 13,000 times less active against PDE5 than tadalafil. Therefore, the concentration of this metabolite is not clinically significant.
Removal
In healthy volunteers, the average clearance of tadalafil when taken orally is 2.5 L/h, and the average half-life is 17.5 hours. Tadalafil is excreted primarily in the form of inactive metabolites, mainly through the intestines (about 61% of the dose) and, to a lesser extent, through the kidneys (about 36% of the dose).
Special groups of patients
Age over 65
Healthy volunteers aged 65 years and older had lower oral clearance of tadalafil, resulting in a 25% increase in the area under the concentration-time curve compared to healthy volunteers aged 19 to 45 years. This difference is not clinically significant and does not require dose adjustment.
Kidney failure
In patients with mild (creatinine clearance 51 to 80 mL/min) and moderate renal impairment (creatinine clearance 31 to 50 mL/min), and in patients with end-stage renal disease on hemodialysis, tadalafil exposure (AUC) was approximately doubled.
In hemodialysis patients, Cmax was 41% higher compared to healthy volunteers. Removal of tadalafil by hemodialysis is negligible.
Liver failure
The pharmacokinetics of tadalafil in patients with mild to moderate hepatic impairment (Child-Pugh class A and B) are comparable to those in healthy volunteers. There is insufficient data for patients with severe hepatic impairment (Child-Pugh class C). When prescribing Tadalafil-SZ to patients with severe liver failure, it is necessary to first assess the risks and benefits of using the drug.
Patients with diabetes
In patients with diabetes mellitus, while taking tadalafil, the area under the concentration-time curve was approximately 19% less than in healthy volunteers. This difference does not require dose adjustment.
Special instructions
Sexual activity has potential risks for patients with cardiovascular disease. Therefore, treatment of erectile dysfunction, including with the drug Tadalafil-SZ, should not be carried out in men with heart diseases for which sexual activity is not recommended.
There are reports of priapism with the use of PDE5 inhibitors, including tadalafil. Patients should be informed to seek immediate medical attention if they experience an erection lasting 4 hours or more. Untimely treatment of priapism leads to damage to the tissue of the penis, which may result in irreversible impotence.
The safety and effectiveness of the combination of Tadalafil-SZ with other PDE5 inhibitors and treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. Like other PDE-5 inhibitors, tadalafil has systemic vasodilatory properties, which may lead to a transient decrease in blood pressure.
Before prescribing Tadalafil-SZ, physicians should carefully consider whether patients with cardiovascular disease would be adversely affected by these vasodilatory effects. Non-arterial anterior ischemic optic neuropathy (NAION) causes visual impairment, including complete loss of vision.
There are rare post-marketing reports of cases of the development of NAPION, temporally associated with the use of PDE-5 inhibitors. IN
It is currently impossible to determine whether there is a direct relationship between the development of NAPION and the use of PDE5 inhibitors or other factors. Doctors should advise patients to stop taking tadalafil and seek medical help if sudden vision loss occurs.
Doctors should also tell patients that people who have had NAPION have an increased risk of developing NAPION again. Patients suspected of having BPH should undergo testing to rule out prostate cancer.
The effectiveness of Tadalafil-SZ in patients undergoing pelvic surgery or radical neurosparing prostatectomy is unknown.
During treatment with Tadalafil-SZ, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Active ingredient
Tadalafil
Composition
1 film-coated tablet contains:
dosage 5 mg:
active ingredient:
tadalafil – 5 mg
excipients (core):
Lactose monohydrate (milk sugar) – 53.8 mg; lactose monohydrate (lactopress) (milk sugar) – 64.0 mg; microcrystalline cellulose – 26.0 mg; croscarmellose sodium (primellose) – 12.5 mg; crospovidone (Kollidon CL-M) – 4.0 mg, crospovidone (Kollidon CL) – 3.0 mg, extra fine hyprolose (hydroxypropylcellulose) – 3.0 mg; hyprolose (hydroxypropylcellulose) – 2.0 mg; sodium stearyl fumarate – 1.5 mg; sodium lauryl sulfate – 0.2 mg;
excipients (shell):
Opadry II 85F22048 yellow – 5 mg (polyvinyl alcohol, partially hydrolyzed – 2.0 mg; titanium dioxide E 171 – 1.0935 mg; macrogol (polyethylene glycol 3350) – 1.01 mg; talc – 0.74 mg; aluminum varnish based on quinoline yellow dye – 0.1505 mg; aluminum varnish based on sunset yellow dye – 0.0035 mg; iron oxide dye (I) yellow E 172 – 0.0015 mg; aluminum varnish based on indigo carmine dye – 0.0010 mg);
Pregnancy
Tadalafil-SZ is not intended for use in women.
Contraindications
Hypersensitivity to tadalafil or any substance included in the drug;
taking medications containing any organic nitrates;
the presence of contraindications to sexual activity in patients with diseases of the cardiovascular system: myocardial infarction within the last 90 days, unstable angina, the occurrence of an attack of angina during sexual intercourse, chronic heart failure class II or higher according to the NYHA classification within the last 6 months, uncontrolled arrhythmias, arterial hypotension (BP < 90/50 mm Hg), uncontrolled arterial hypertension, ischemic stroke within the last 6 months;
loss of vision due to non-arteritic anterior ischemic optic neuropathy (NAPION) (regardless of the connection with taking PDE-5 inhibitors);
simultaneous use with doxazosin, other PDE-5 inhibitors, other drugs for the treatment of erectile dysfunction, with guanylate cyclase stimulators, such as riociguat;
chronic renal failure (Cl creatinine < 30 ml/min);
lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
age up to 18 years.
With caution:severe liver failure (class C according to the Child-Pugh classification) (there is insufficient data on such patients); simultaneous use of alpha1-blockers (simultaneous use of these drugs can lead to symptomatic arterial hypotension in some patients; when using a single dose of tadalafil, symptomatic hypotension is not observed when used simultaneously with tamsulosin, a selective alpha1A-blocker (see “Interactions”);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 inhibitors of the CYP3A4 isoenzyme (including ritonavir, saquinavir, ketoconazole, itraconazole, clarithromycin, erythromycin, grapefruit juice), antihypertensive drugs, 5-alpha reductase inhibitors.Diagnosis of erectile dysfunction should include identification of the potential underlying cause, appropriate medical examination, and determination of treatment strategy.
Side Effects
The most common adverse events in patients with erectile dysfunction and BPH are headache and dyspepsia, as well as back pain and myalgia.
In accordance with the WHO classification, all reactions are distributed according to organ system and frequency of development: very often (> 1/10); often (> 1/100, 1/1000, 1U0000, < 11000); very rare (< 1/10000), frequency unknown (it is impossible to determine the frequency of occurrence of reactions from the available data).
Immune system disorders:
Uncommon: hypersensitivity reactions. Rarely: angioedema. Nervous system disorders:
Common: headache.
Uncommon: dizziness.
Rarely: stroke (including acute cerebrovascular accident (ACVA) of the hemorrhagic type), fainting, transient ischemic attacks, migraine, epileptic seizures, transient amnesia.
Visual disorders:
Uncommon: blurred vision, pain in the eyeball.
Rarely: visual field impairment, eyelid swelling, conjunctival hyperemia, non-arterial anterior ischemic optic neuropathy, retinal vascular occlusion.
Hearing and labyrinthine disorders:
Uncommon: ringing in the ears.
Rare: sudden hearing loss.
Cardiac disorders:
Uncommon: palpitations, tachycardia.
Rarely: myocardial infarction, ventricular arrhythmias, unstable angina.
Vascular disorders: Common: flushing of blood to the face.
Uncommon: decreased blood pressure, increased blood pressure.
Disorders of the respiratory system, chest and mediastinal organs:
Common: nasal congestion.
Uncommon: shortness of breath, nosebleeds.
Gastrointestinal disorders:
Common: dyspepsia.
Uncommon: abdominal pain, gastroesophageal reflux, diarrhea in patients over 65 years of age, vomiting, nausea.
Disorders of the skin and subcutaneous tissues:
Uncommon: rash.
Rarely: urticaria, Stevens-Johnson syndrome, exfoliative dermatitis, hyperhidrosis (excessive sweating).
Musculoskeletal and connective tissue disorders:
Common: back pain, myalgia, pain in the extremities. Renal and urinary tract disorders: Uncommon: hematuria.
Genital and breast disorders: Uncommon: prolonged erection.
Rarely: priapism, hematospermia, bleeding from the penis.
General disorders:
Uncommon: chest pain, peripheral edema, fatigue. Rare: facial swelling, sudden cardiac death.
’Observed in patients with pre-existing cardiovascular risk factors. However, it is not possible to accurately determine whether these events are directly related to these risk factors, to tadalafil, to sexual arousal, or to a combination of these or other factors.
Adverse reactions identified during post-marketing use that were not observed during clinical placebo-controlled studies.
More frequently observed when tadalafil was used in patients already taking antihypertensive agents.
Interaction
Effect of other drugs on tadalafil
Tadalafil is mainly metabolized with the participation of the CYP3A4 isoenzyme. The selective inhibitor of the CYP3A4 isoenzyme ketoconazole (400 mg per day) increases the exposure of a single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketoconazole (200 mg per day) increases the exposure of a single dose of tadalafil (AUC) by 107% and Cmax by 15% relative to AUC and Cmax values for tadalafil alone.
Ritonavir (200 mg twice daily), an inhibitor of CYP3A4, 2C9, 2C19 and 2D6, increases single-dose tadalafil exposure (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 inhibitors, such as erythromycin, clarithromycin, and itraconazole and grapefruit juice, may increase tadalafil plasma concentrations. The role of transporters (eg, P-glycoprotein) in the distribution of tadalafil is unknown.
The potential for drug interactions mediated by transporter inhibition exists. A selective inducer of the CYP3A4 isoenzyme, rifampicin (at a dose of 600 mg per day), reduces the exposure of a single dose of tadalafil (AUC) by 88% and Cmax by 46%, relative to the AUC and Cmax values for tadalafil alone.
It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) should also reduce tadalafil plasma concentrations.
Concomitant use of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the AUC of tadalafil.
An increase in gastric pH as a result of taking the H2-histamine receptor blocker nizatidine did not affect the pharmacokinetics of tadalafil.
The safety and effectiveness of combining tadalafil with other treatments for erectile dysfunction or other PDE5 inhibitors has not been studied and the use of such combinations is not recommended.
Effect of tadalafil on other drugs
Tadalafil is known to enhance 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 (NO) and cGMP. Therefore, the use of tadalafil while taking nitrates is contraindicated.
Tadalafil does not have a clinically significant effect on the clearance of drugs whose metabolism occurs with the participation of cytochrome P450. Studies have confirmed that tadalafil does not inhibit or induce the isoenzymes CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP2E1. Tadalafil does not have a clinically significant effect on the AUC of S-warfarin or R-warfarin. Tadalafil does not affect the effect of warfarin on prothrombin time.
Tadalafil does not potentiate an increase in the duration of bleeding caused by taking acetylsalicylic acid.
Tadalafil has systemic vasodilatory properties and may enhance the effect of antihypertensive drugs aimed at lowering blood pressure. Additionally, patients taking multiple antihypertensive agents and whose hypertension was poorly controlled experienced a slightly greater reduction in blood pressure.
In the vast majority of patients, this decrease was not associated with hypotensive symptoms. Patients treated with antihypertensive drugs and taking tadalafil should be given appropriate clinical advice. There was no significant reduction in blood pressure with the simultaneous use of tadalafil and the selective alpha1A-blocker tamsulosin in healthy volunteers.
Concomitant use of tadalafil with doxazosin is contraindicated. When tadalafil was administered to healthy volunteers taking doxazosin (4-8 mg per day), an alpha]-adrenergic blocker, an increase in the hypotensive effect of doxazosin was observed. Some patients experienced symptoms associated with low blood pressure, including fainting.
Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated because Riociguat enhances the hypotensive effect of PDE5 inhibitors.
Drug interaction studies have not been conducted with tadalafil and 5-alpha reductase inhibitors; caution should be exercised when taking them simultaneously.
Tadalafil causes an increase in the bioavailability of ethinyl estradiol when taken orally.
A similar increase in bioavailability can be expected with terbutaline, but the clinical implications have not been established.
Tadalafil did not affect the concentration of alcohol, nor did alcohol affect the concentration of tadalafil. At high doses of alcohol (0.7 g/kg), taking tadalafil did not cause a statistically significant decrease in mean blood pressure. Postural dizziness and orthostatic hypotension have been observed in some patients.
When taking tadalafil in combination with lower doses of alcohol (0.6 g/kg), no decrease in blood pressure was observed, and dizziness occurred with the same frequency as when taking alcohol alone.
Tadalafil does not have a clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.
Overdose
Symptoms: with a single dose of tadalafil administered to healthy volunteers 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.
Storage conditions
In a place protected from light, at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
Shelf life
3 years.
Manufacturer
North Star NAO, Russia
Shelf life | 3 years. |
---|---|
Conditions of storage | In the dark place at a temperature not exceeding 25 °С. Store out of the reach of children. |
Manufacturer | North Star NAO, Russia |
Medication form | pills |
Brand | North Star NAO |
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