Talafil

Tadalafil.

TALAFIL-5: Each film coated tablet contains: Tadalafil 5 mg.
TALAFIL-10: Each film coated tablet contains: Tadalafil 10 mg.
TALAFIL-20: Each film coated tablet contains: Tadalafil 20 mg.

Pharmacology: Pharmacodynamics: Tadalafil is a selective inhibitor of phosphodiesterase type 5 (PDE5). When sexual stimulation causes the local release of nitric oxide in the corpus cavernosum, nitric oxide activates the enzyme guanylate cyclase, which stimulates the synthesis of cyclic guanosine monophosphate (cGMP). cGMP produces smooth muscle relaxation and increased blood flow into the corpora cavernosa, thereby producing an erection. Tadalafil has no effect in the absence of sexual stimulation.
Tadalafil is > 10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4 and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leucocytes, skeletal muscle, and other organs. Tadalafil is > 10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Tadalafil is >700-fold more potent for PDE5 than for PDE6, which is found in the retina and phototransduction. Tadalafil is > 9,000-fold more potent for PDE5 than PDE8, PDE9, PDE10 and 14-fold more potent for PDE5 than PDE11.
5 mg Tablet: The effect of PDE5 inhibitors on cGMP concentration in the corpus cavernosum is also observed in the smooth muscle of prostate and bladder. The resulting vascular relaxation increase blood perfusion.
Pharmacokinetics: Absorption: Tadalafil is readily absorbed after oral administration and the mean maximum observed plasma concentration (Cmax) is achieved at a median time of 2 hours after dosing. Absolute bioavailability of tadalafil following oral dosing has not been determined. The rate and extent of absorption of tadalafil are not influenced by food.
Distribution: The mean volume of distribution is approximately 63 liters. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins. Less than 0.0005% of the administered dose appeared in the semen of healthy subjects.
Metabolism: Tadalafil is predominantly metabolised by the cytochrome P450 (CYP) 3A4 isoform. The major circulating metabolite is the methylcatechol glucuronide. It is not expected to be clinically active at observed metabolite concentrations.
Elimination: The mean oral clearance for tadalafil is 2.5 L/h and the mean half-life is 17.5 hours in healthy subjects. Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).

Treatment of erectile dysfunction in adult males.
In order for tadalafil to be effective for the treatment of erectile dysfunction, sexual stimulation is required.
TALAFIL is not indicated for use by women.
5 mg Tablet: Treatment of the sign and symptoms of benign prostatic hyperplasia in adult males including those with erectile dysfunction.

Recommended Dose: Erectile dysfunction in adult men: The recommended dose is 10 mg taken prior to anticipated sexual activity and without regard to 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.
5 mg Tablet: Tadalafil 10 and 20 mg is intended for use prior to anticipated sexual activity and is not recommended for continuous daily use.
In responder patients to on-demand regimen who anticipate a frequent use of tadalafil (i.e., at least twice weekly) a once daily regimen with the lowest doses of tadalafil might be considered suitable, based on patient choice and the physician's judgement.
In these patients, the recommended dose is 5 mg taken once a day at approximately the same time of day. The dose may be decreased to 2.5 mg once a day based on individual tolerability.
The appropriateness of continued use of the daily regimen should be reassessed periodically.
10 mg & 20 mg Tablet: Continuous daily use of the medication is strongly discouraged because the long-term safety after prolonged daily dosing has not been established and also because the effect of tadalafil usually lasts for long than one day.
Benign prostatic hyperplasia in adult men (for 5 mg only): The recommended dose is 5 mg, taken at approximately the same time every day with or without food. For adult men being treated for both benign prostatic hyperplasia and erectile dysfunction the recommended dose is also 5 mg taken at approximately the same time every day.
Use in elderly men: Dose adjustments are not required in elderly patients.
Use in men with impaired renal function: 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 (for on-demand treatment for 5 mg).
5 mg Tablet: Once-a-day dosing of 2.5 or 5 mg tadalafil both for the treatment of erectile dysfunction or benign prostatic hyperplasia is not recommended in patients with severe renal impairment.
Use in men with impaired hepatic function: 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.
5 mg Tablet: 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.
Once-a-day dosing both for the treatment of erectile dysfunction and benign prostatic hyperplasia has not been evaluated in patients with hepatic impairment; therefore, if prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.
10 mg & 20 mg Tablet: The recommended dose is 10 mg taken prior to anticipated sexual activity and without regard to food.
Use in men with diabetes: Dose adjustments are not required in diabetic patients.
Use in children and adolescents: Tadalafil should not be used in individual below 18 years of age.
Mode of administration: Tadalafil is administered orally and without regard to meals.

Symptoms: Single doses 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.
Management: In cases of overdose, standard supportive measures should be adopted, as required. Renal dialysis is not expected to accelerate clearance as these drugs are highly bound to plasma proteins and are not significantly eliminated in urine.

Hypersensitivity to tadalafil or any of the excipients.
Concomitant use of tadalafil and organic nitrate or nitrate are contraindicated.
Should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.
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.
5 mg Tablet: Tadalafil is contraindicated in patients who had a history of loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION).

This medicine is not used for sexual stimulation.
Contraindication with patients who have cardiovascular disease that take nitrate vasodilator agent because it may be fatal, death.
Contraindication in children and women, patients who have liver disease or renal disease.
Should not use this medicine more than once daily.
Should not use this medicine with other medicine in erectile dysfunction.
If visual disturbance, bone pain, chest pain, palpitation, arrhythmia, sweating or fainting occurs, consult the doctor immediately.

Assess the cardiovascular status of the patient prior to initiating tadalafil therapy.
Serious cardiovascular event, including myocardial infarction, sudden cardiac death, unstable angina, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, palpitations, and tachycardia, have been reported in temporal association with tadalafil during postmarketing experience. In addition hypertension were also reported. Most of the patients 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.
Non-arteritic anterior ischemic optic neuropathy (NAION) is a cause of decreased vision, including permanent vision loss that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. It is not possible to determine if these events are related directly to the use of PDE5 inhibitors or other factors. Instruct patients to seek medical assistance for sudden loss of vision. Clinicians should discuss the increased risk of NAION with patients who have already experienced NAION.
Combined use of tadalafil and other PDE5 inhibitors have not been studied. Therefore, the use of such combination is not recommended.
There is insufficient data available in patients with severe hepatic impairment (Child-Pugh class C).
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.
Should be used with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease), or who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, leukemia).
Caution should be exercised when prescribing tadalafil to patients who are taking alpha-blockers. In some patients, concomitant use of both drug class may lead to symptomatic hypotension in some patient.
Caution should be exercised when prescribing tadalafil to patients using potent CYP3A4 inhibitors (such as protease inhibitors, ketoconazole, itraconazole) as increase plasma concentration (AUC) for tadalafil.
Combined use of tadalafil and other therapies for erectile dysfunction currently is not recommended because safety and efficacy of such combinations have not been studied.

Pregnancy: Pregnancy category B.
Tadalafil is not indicated for use by women. There are no study of tadalafil in pregnant woman.
Lactation: It is not known if the drugs are excreted in human breast milk. Tadalafil is not indicated for use by women.

5 mg Tablet: Immune system disorders: Uncommon: Hypersensitivity reactions.
Nervous system disorders: Common: Headache. Uncommon: Dizziness. Rare: Stroke, Syncope, Migraine Seizures, Transient amnesia.
Eye disorder: Uncommon: Blurred vision, Eye pain. Rare: Visual field defect, Swelling of eyelids, Conjunctivitis hyperaemia, Non-arteritic anterior ischaemic optic neuropathy (NAION), Retinal vascular occlusion.
Ear and labyrinth disorders: Rare: Sudden deafness.
Cardiac disorders: Uncommon: Tachycardia, Palpitations. Rare: Myocardial infarction, Unstable angina pectoris.
Vascular disorders: Common: Flushing. Uncommon: Hypotension, Hypertension.
Respiratory, thoracic and mediastinal disorders: Common: Nasal congestion. Uncommon: Epistaxis, Dyspnoea.
Gastrointestinal disorders: Common: Dyspepsia. Uncommon: Abdominal pain, Gastro-oesophageal reflux.
Skin and subcutaneous tissue disorders: Uncommon: Rash, Hyperhidrosis (sweating). Rare: Urticaria, Stevens-Johnson syndrome, Exfoliative dermatitis.
Musculoskeletal and connective tissue disorders: Common: Back pain, Myalgia.
Reproductive system and breast disorders: Rare: Priapism.
General disorders and administration site conditions: Uncommon: Chest pain. Rare: Facial oedema, Sudden cardiac death.
10 mg & 20 mg Tablet: Immune system disorders: Uncommon: Hypersensitivity reactions.
Nervous system disorders: Very common: Headache. Common: Dizziness. Rare: Stroke, Syncope, Transient ischaemic attacks, Migraine. Not known: Seizures, Amnesia.
Eye disorder: Uncommon: Blurred vision, Eye pain, Swelling of eyelids, Conjunctival hyperaemia. Rare: Visual field defect. Not known: Non-arteritic anterior ischaemic optic neuropathy (NAION).
Ear and labyrinth disorders: Not known: Sudden deafness.
Cardiac disorders: Common: Palpitations. Uncommon: Tachycardia. Rare: Myocardial infarction. Not known: Unstable angina pectoris, Ventricular arrhythmia.
Vascular disorders: Common: Flushing. Uncommon: Hypotension.
Respiratory, thoracic and mediastinal disorders: Common: Nasal congestion. Uncommon: Dyspnoea, Epistaxis.
Gastrointestinal disorders: Very common: Dyspepsia. Common: Abdominal pain, Gastro-oesophageal reflux.
Skin and subcutaneous tissue disorders: Uncommon: Rash, Urticaria, Hyperhidrosis (sweating). Not known: Stevens-Johnson syndrome, Exfoliative dermatitis.
Musculoskeletal and connective tissue disorders: Common: Back pain, Myalgia.
Reproductive system and breast disorders: Rare: Prolonged erections.
General disorders and administration site conditions: Uncommon: Chest pain. Rare: Facial oedema. Not known: Sudden cardiac death.

Organic Nitrates and Nitric Oxide Donors: Administration of tadalafil to patients who are using any form of organic nitrate is contraindicated. Based on pharmacodynamic interaction were potential increase in hypotensive effect. Additive effects was observed when sublingual nitroglycerin followed a tadalafil dose, with most effects no longer detectable after 48 hours.
Drug affecting hepatic microsomal enzymes: Tadalafil does not appear to induce or inhibit the clearance of other drugs metabolized by CYP isoform CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
Warfarin: No clinical effect on pharmacokinetic and pharmacodynamic of warfarin. Tadalafil had no effect on S- or R-warfarin, nor did affect changes in prothrombin time induced by warfarin.
Aspirin: No clinical effect on pharmacodynamic such as alteration bleeding time caused by aspirin.
Antihypertensive Agents: Potentiation of hypotensive effect based on pharmacodynamic interaction with antihypertensive agents (alpha-adrenergic blocking agents, angiotensin II receptor antagonists, amlodipine, enalapril, metoprolol). In some patients, concomitant use of tadalafil and alpha-adrenergic blocking agents can lower blood pressure.
Alcohol: No clinical effect on the pharmacokinetics of tadalafil and alcohol plasma concentration. In addition, coadministration of tadalafil and alcohol may produce postural dizziness and orthostatic hypotension.
Theophylline: Potential pharmacodynamic interaction. The only small effect is theophylline-induced increase in heart rate.
H2-antagonist: Nizatidine had no clinically effects on pharmacokinetics.
Antacid: Coadministration of tadalafil and antacids reduced the rate of tadalafil absorption without altering the AUC.

Store below 30°C.

Drugs for Erectile Dysfunction & Ejaculatory Disorders

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

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