TADALAFIL TABLETS Composition: Each film coated tablet contains: Tadalafil 20 mg Mechanism Of Action: Tadalafil is a selective, reversible inhibitor

of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5). When sexual stimulation causes the local release of nitric oxide, inhibition of PDE5 by tadalafil produces increased levels of cGMP in the corpus cavernosum. This results in smooth muscle relaxation and inflow of blood into the penile tissues, thereby producing an erection. Tadalafil has no effect in the absence of sexual stimulation. Pharmacological Information: Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil inhibits PDE5. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by Tadalafil has no effect in the absence of sexual stimulation. Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas. Pharmacokinetics: Tadalafil is well absorbed after a dose by mouth. Peak plasma concentrations are attained within 2 hours; the rate and extent of absorption are not affected by food. Tadalafil is widely distributed into tissues and is about 94% bound to plasma proteins. It is metabolised in the liver mainly by the cytochrome P450 isoenzyme CYP3A4. The major metabolite, the methylcatechol glucuronide, is inactive. The mean half-life of tadalafil is about 17.5 hours. Tadalafil is excreted, mainly as metabolites, in the faeces (61% of the dose), and to a lesser extent the urine (36% of the dose). Clearance may be reduced in the elderly and in patients with renal impairment. Indication: T-Max is indicated for the treatment of erectile dysfunction. In order for Tadalafil Tablets to be effective, sexual stimulation is required. Tadalafil Tablet is not indicated for use by women. Side Effects: Side effects most commonly reported from Tadalafil are headache, flushing, and dyspepsia. There may be visual disturbances, dizziness, and nasal congestion. Other adverse effects reported include diarrhoea, vomiting, swelling of the eyelids, pain and redness of the eyes, epistaxis, muscle pain, back pain, skin rashes, urinary-tract infection, syncope, cerebrovascular haemorrhage, and transient ischaemic attack. Priapism has also occurred. There have also been reports of palpitations and serious cardiovascular events, associated with the use of tadalafil. Contra-indications: Administration of Tadalafil to patients who are using any form of organic nitrate is contra indicated. Agents for the treatment of erectile dysfunction, including Tadalafil, should 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. Tadalafil is therefore contra indicated in the following groups of patients: 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 mm Hg), or uncontrolled hypertension. Patients with a stroke within the last 6 months. Tadalafil is also contra indicated 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. Tadalafil should not be used in patients with hypersensitivity to tadalafil or to any of the excipients. Drug Interaction: Tadalafil or other phosphodiesterase type-5 inhibitors may potentiate the hypotensive effects of organic nitrates, and are therefore contra-indicated in patients receiving such drugs. Tadalafil may also enhance the hypotensive effect of nicorandil and use of the two drugs together should be avoided. Symptomatic hypotension may also occur when phosphodiesterase type-5 inhibitors are given with alpha blockers. Generally, the patient should be stabilised on alpha blocker therapy before the phosphodiesterase type-5 inhibitor is started at a low dose and adjusted according to response; minimum dosage intervals have also been recommended in some cases. Drugs that inhibit the cytochrome P450 isoenzyme CYP3A4, such as cimetidine, delavirdine, erythromycin, itraconazole, ketoconazole, and HIV-protease inhibitors, may reduce the clearance of phosphodiesterase type-5 inhibitors, necessitating a reduction in dosage. Furthermore, plasma concentrations of phosphodiesterase type-5 inhibitors are significantly increased by ritonavir, requiring even greater dosage reduction, and such combinations should not be given unless absolutely essential. Grapefruit juice should be avoided with tadalafil or other phosphodiesterase type-5 inhibitors as it may increase their plasma concentrations. Inducers of CYP3A4, such as rifampicin, are likely to decrease plasma concentrations of phosphodiesterase type-5 inhibitors. Rifampicin, an inducer of the cytochrome P450 isoenzyme CYP3A4, has been shown to decrease the plasma concentrations of tadalafil. Dosage: The recommended starting dose of T-Max Tablet in most patients is 20 mg, taken prior to anticipated sexual activity. The dose may be decreased to 10 mg, based on individual efficacy and tolerability. The maximum recommended dosing frequency is once per day in most patients. Tadalafil Tablet was shown to improve erectile function compared to placebo up to 36 hours following

dosing. Therefore, when advising patients on optimal use of Tadalafil Tablet, this should be taken into consideration. Tadalafil Tablet may be taken without regard to food. STORAGE: Store in a cool and dry place, protect from light. Keep out of the reach of children. PACKAGING: 1 x 4 tablets in blisters.