Tadalafil Stella

Tadalafil.

Active ingredient: Tadalafil 20 mg.
Excipients/Inactive Ingredients: Lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, hydroxypropyl cellulose, magnesium stearate, hypromellose, macrogol 6000, talc, titanium dioxide, yellow ferric oxide.

Treatment of erectile dysfunction in adult males. In order for tadalafil to be effective for the treatment of erectile dysfunction, sexual stimulation is required.

Administration: Oral use.
Dosage: Erectile dysfunction in adult men: In general, the recommended dose is 10 mg taken prior to anticipated sexual activity and with or without food.
In those patients in whom tadalafil 10 mg does not produce an adequate effect, 20 mg might be tried. It may be taken at least 30 minutes prior to sexual activity.
The maximum dose frequency is once per day.
Tadalafil 10 and 20 mg is intended for use prior to anticipated sexual activity and it is not recommended for continuous daily use.
Special populations: Elderly men: Dose adjustments are not required in elderly patients.
Men with renal impairment: Dose adjustments are not required in patients with mild to moderate renal impairment. For patients with severe renal impairment, 10 mg is the maximum recommended dose.
Men with hepatic impairment: For the treatment of erectile dysfunction using on-demand tadalafil, the recommended dose of tadalafil is 10 mg taken prior to anticipated sexual activity and with or without food. There is limited clinical data on the safety of tadalafil in patients with severe hepatic impairment (Child-Pugh class C); if prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician. There are no available data about the administration of doses higher than 10 mg of tadalafil to patients with hepatic impairment.
Men with diabetes: Dose adjustments are not required in diabetic patients.
Paediatric population: There is no relevant use of tadalafil in the paediatric population with regard to the treatment of erectile dysfunction.

Single doses of up to 500 mg have been given to healthy subjects, and multiple daily doses up to 100 mg have been given to patients. Adverse events were similar to those seen at lower doses.
In cases of overdose, standard supportive measures should be adopted, as required. Haemodialysis contributes negligibly to tadalafil elimination.

Hypersensitivity to the active substance or to any of the excipients of the product.
In clinical studies, tadalafil was shown to augment the hypotensive effects of nitrates. This is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway. Therefore, administration of tadalafil to patients who are using any form of organic nitrate is contraindicated.
Tadalafil must not be used in men with cardiac disease for whom sexual activity is inadvisable. Physicians should consider the potential cardiac risk of sexual activity in patients with pre-existing cardiovascular disease.
The following groups of patients with cardiovascular disease were not included in clinical trials and the use of tadalafil is therefore contraindicated: patients with myocardial infarction within the last 90 days; patients with unstable angina or angina occurring during sexual intercourse; patients with New York Heart Association Class 2 or greater heart failure in the last 6 months; patients with uncontrolled arrhythmias, hypotension (<90/50 mmHg), or uncontrolled hypertension; patients with a stroke within the last 6 months.
Tadalafil is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure.
The co-administration of PDE5 inhibitors, including tadalafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension.

Before treatment with tadalafil: A medical history and physical examination should be undertaken to diagnose erectile dysfunction and determine potential underlying causes, before pharmacological treatment is considered.
Prior to initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Tadalafil has vasodilator properties, resulting in mild and transient decreases in blood pressure and as such potentiates the hypotensive effect of nitrates.
The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following an appropriate medical assessment. It is not known if tadalafil is effective in patients who have undergone pelvic surgery or radical non-nerve-sparing prostatectomy.
Cardiovascular: Serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina pectoris, ventricular arrhythmia, stroke, transient ischaemic attacks, chest pain, palpitations and tachycardia, have been reported either post-marketing and/or in clinical trials. Most of the patients in whom these events have been reported had pre-existing cardiovascular risk factors. However, it is not possible to definitively determine whether these events are related directly to these risk factors, to tadalafil, to sexual activity, or to a combination of these or other factors.
In patients who are taking alpha₁ blockers, concomitant administration of tadalafil may lead to symptomatic hypotension in some patients. The combination of tadalafil and doxazosin is not recommended.
Vision: Visual defects and cases of NAION have been reported in connection with the intake of tadalafil and other PDE5 inhibitors. Analyses of observational data suggest an increased risk of acute NAION in men with erectile dysfunction following exposure to tadalafil or other PDE5 inhibitors. As this may be relevant for all patients exposed to tadalafil, the patient should be advised that in case of sudden visual defect, he should stop taking tadalafil and consult a physician immediately.
Decreased or sudden hearing loss: Cases of sudden hearing loss have been reported after the use of tadalafil. Although other risk factors were present in some cases (such as age, diabetes, hypertension and previous hearing loss history), patients should be advised to stop taking tadalafil and seek prompt medical attention in the event of sudden decrease or loss of hearing.
Hepatic impairment: There is limited clinical data on the safety of single-dose administration of tadalafil in patients with severe hepatic insufficiency (Child-Pugh Class C). If tadalafil is prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.
Priapism and anatomical deformation of the penis: Patients who experience erections lasting 4 hours or more should be instructed to seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.
Tadalafil should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease) or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).
Use with CYP3A4 inhibitors: Caution should be exercised when prescribing tadalafil to patients using potent CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, and erythromycin), as increased tadalafil exposure (AUC) has been observed if the medicinal products are combined.
Tadalafil and other treatments for erectile dysfunction: The safety and efficacy of combinations of tadalafil and other PDE5 inhibitors or other treatments for erectile dysfunction have not been studied. The patients should be informed not to take tadalafil in such combinations.
Lactose: Tadalafil STELLA Tablets 20mg contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: Tadalafil has negligible influence on the ability to drive or use machines. Although the frequency of reports of dizziness in placebo and tadalafil arms in clinical trials was similar, patients should be aware of how they react to tadalafil before driving or using machines.

Tadalafil is not indicated for use by women.
Pregnancy: There are limited data from the use of tadalafil in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of tadalafil during pregnancy.
Lactation: Available pharmacodynamic/toxicological data in animals have shown excretion of tadalafil in milk. A risk to the suckling child cannot be excluded. Tadalafil should not be used during breastfeeding.

Frequency convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000) and Not known (cannot be estimated from the available data).
Immune system disorders: Uncommon: Hypersensitivity reactions.
Rare: Angioedema.
Nervous system disorders: Common: Headache.
Uncommon: Dizziness.
Rare: Stroke (including haemorrhagic events), syncope, transient ischaemic attacks, migraine, seizures, transient amnesia.
Eye disorders: Uncommon: Blurred vision, sensations described as eye pain.
Rare: Visual field defect, swelling of eyelids, conjunctival hyperaemia, non-arteritic anterior ischaemic optic neuropathy (NAION), retinal vascular occlusion.
Ear and labyrinth disorders: Uncommon: Tinnitus.
Rare: Sudden hearing loss.
Cardiac disorders: Uncommon: Tachycardia, palpitations.
Rare: Myocardial infarction, unstable angina pectoris, ventricular arrhythmia.
Vascular disorders: Common: Flushing.
Uncommon: Hypotension, hypertension.
Respiratory, thoracic and mediastinal disorders: Common: Nasal congestion.
Uncommon: Dyspnoea, epistaxis.
Gastrointestinal disorders: Common: Dyspepsia.
Uncommon: Abdominal pain, vomiting, nausea, gastro-oesophageal reflux.
Skin and subcutaneous tissue disorders: Uncommon: Rash.
Rare: Urticaria, Stevens-Johnson syndrome, exfoliative dermatitis, hyperhidrosis (sweating).
Musculoskeletal and connective tissue disorders: Common: Back pain, myalgia, pain in extremity.
Renal and urinary disorders: Uncommon: Haematuria.
Reproductive system and breast disorders: Uncommon: Prolonged erections.
Rare: Priapism, penile haemorrhage, haematospermia.
General disorders and administration site conditions: Uncommon: Chest pain, peripheral oedema, fatigue.
Rare: Facial oedema, sudden cardiac death.

Effects of other substances on tadalafil: Cytochrome P450 inhibitors: Tadalafil is principally metabolised by CYP3A4. A selective inhibitor of CYP3A4, ketoconazole (200 mg daily), increased tadalafil (10 mg) exposure (AUC) 2-fold and C_max by 15%, relative to the AUC and C_max values for tadalafil alone. Ketoconazole (400 mg daily) increased tadalafil (20 mg) exposure (AUC) 4-fold and C_max by 22%. Ritonavir, a protease inhibitor (200 mg twice daily), which is an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil (20 mg) exposure (AUC) 2-fold with no change in C_max. Although specific interactions have not been studied, other protease inhibitors, such as saquinavir, and other CYP3A4 inhibitors, such as erythromycin, clarithromycin, itraconazole, and grapefruit juice, should be co-administered with caution, as they would be expected to increase plasma concentrations of tadalafil. Consequently, the incidence of the adverse reactions might be increased.
Transporters: The role of transporters (for example, p-glycoprotein) in the disposition of tadalafil is not known. Therefore, there is the potential of drug interactions mediated by inhibition of transporters.
Cytochrome P450 inducers: A CYP3A4 inducer, rifampicin, reduced tadalafil AUC by 88%, relative to the AUC values for tadalafil alone (10 mg). This reduced exposure can be anticipated to decrease the efficacy of tadalafil; the magnitude of decreased efficacy is unknown. Other inducers of CYP3A4, such as phenobarbital, phenytoin, and carbamazepine, may also decrease plasma concentrations of tadalafil.
Effects of tadalafil on other medicinal products: Nitrates: In clinical studies, tadalafil (10 and 20 mg) was shown to augment the hypotensive effects of nitrates. Therefore, administration of tadalafil to patients who are using any form of organic nitrate is contraindicated. Based on the results of a clinical study in which 150 subjects receiving daily doses of tadalafil 20 mg for 7 days and 0.4 mg sublingual nitroglycerin at various times, this interaction lasted for more than 24 hours and was no longer detectable when 48 hours had elapsed after the last tadalafil dose. Thus, in a patient prescribed any dose of tadalafil, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should have elapsed after the last dose of tadalafil before nitrate administration is considered. In such circumstances, nitrates should only be administered under close medical supervision with appropriate haemodynamic monitoring.
Anti-hypertensives (including calcium channel blockers): The co-administration of doxazosin (4 and 8 mg daily) and tadalafil (20 mg as a single dose) increases the blood pressure-lowering effect of this alpha-blocker in a significant manner. This effect lasts at least twelve hours and may be symptomatic, including syncope. Therefore, this combination is not recommended.
Riociguat: Preclinical studies showed an additive systemic blood pressure-lowering effect when PDE5 inhibitors were combined with riociguat. In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated.
CYP1A2 substrates (e.g. theophylline): When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) in a clinical pharmacology study, there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 bpm) increase in heart rate. Although this effect is minor and was of no clinical significance in this study, it should be considered when co-administering these medicinal products.
Ethinylestradiol and terbutaline: Tadalafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline, although the clinical consequence of this is uncertain.
Alcohol: Alcohol concentrations (mean maximum blood concentration 0.08%) were not affected by co-administration with tadalafil (10 mg or 20 mg). In addition, no changes in tadalafil concentrations were seen 3 hours after co-administration with alcohol. Alcohol was administered in a manner to maximise the rate of alcohol absorption (overnight fast with no food until 2 hours after alcohol). Tadalafil (20 mg) did not augment the mean blood pressure decrease produced by alcohol (0.7 g/kg or approximately 180 ml of 40% alcohol [vodka] in an 80 kg male) but, in some subjects, postural dizziness and orthostatic hypotension were observed. When tadalafil was administered with lower doses of alcohol (0.6 g/kg), hypotension was not observed and dizziness occurred with similar frequency to alcohol alone. The effect of alcohol on cognitive function was not augmented by tadalafil (10 mg).
Cytochrome P450-metabolised medicinal products: Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal products metabolised by CYP450 isoforms. Studies have confirmed that tadalafil does not inhibit or induce CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
CYP2C9 substrates (e.g. R-warfarin): Tadalafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin (CYP2C9 substrate), nor did tadalafil affect changes in prothrombin time induced by warfarin.
Aspirin: Tadalafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetylsalicylic acid.
Antidiabetic medicinal products: Specific interaction studies with antidiabetic medicinal products were not conducted.

Store in a well-closed container, in a dry place. Do not store above 30°C.

Drugs for Erectile Dysfunction & Ejaculatory Disorders

G04BE08 - tadalafil ; Belongs to the class of drugs used in erectile dysfunction.

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