SIDNAKIND Tablet

For the treatment of erectile dysfunction which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance.

Dosage and Administration

Use in adults over 18 years

The recommended dose is 50mg taken as needed approximately 1 hour before sexual activity. Based on efficacy and toleration, the dose may be increased to 100mg or decreased to 25mg. The maximum recommended dose is 100mg. The maximum recommended dosing frequency is once per day. Onset of effect may be delayed if taken with food.

See the package insert about the details below:

- Use in patients with impaired renal function

- Use in patients with impaired hepatic function

- Use in children and adolescents

- Use in patients using other medicines.

Mode of Administration: For oral use.

Hypersensitivity to the active substance or to any of the excipients.

Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, Sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors (such as amyl nitrate) or nitrates in any form is therefore contraindicated.

Agents for the treatment of erectile dysfunction, including Sildenafil, should not be used in men for whom sexual activity is inadvisable (e.g. patients with severe cardiovascular disorders such as unstable angina or severe cardiac failure).

Sildenafil is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy, regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure.

The safety of Sildenafil has not been studied in the following sub-group of patients and its use is therefore contraindicated: severe hepatic impairment, hypotension (blood pressure <90/50 mmHg), recent history of stroke or myocardial infarction and known hereditary degenerative retinal disorders such as retinitis pigmnentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

Adverse effects most commonly reported with Sildenafil are headache, flushing, and dyspepsia. Also common are visual disturbances such as blurred vision, photophobia, chromatopsia, cyanopsia, eye irritation, pain and redness of the eyes. Retinal haemorrhage has occurred, and non-arteritic anterior ischaemic optic neuropathy causing permanent loss of vision has been reported rarely. Other common adverse effects include dizziness, insomnia, anxiety, vertigo, epistaxis, nasal congestion, pyrexia, and gastrointestinal disturbances such as diarrhoea and vomiting. Priapism can occur. Other adverse effects include skin rashes, erythema, alopenia, limb and/or back pain, myalgia, facial oedema, fluid retention, paraesthesia, and urinary-tract infection. Dyspnoea, cough, rhinitis, sinusitis, bronchitis, and cellulitis can occur. Sudden decrease or loss of hearing has been reported. Other reported effects include anaemia, leucopenia, gynaecomastia, urinary frequency or incontinence, haematuria, and seizures. Cerebrovascular haemorrhage and transient ischaemic attacks have occurred. There have also been reports of palpitations, syncope, hypertension, hypotension, and serious cardiovascular events including myocardial infarction, arrhythmias, tachycardia, unstable angina, and sudden cardiac death.

Sildenafil or other phosphodiesterase type-5 inhibitors may potentiate the hypotensive effects of organic nitrates, and are therefore contra-indicated in patients receiving such drugs.

Sildenafil may also enhance the hypotensive effect f 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 stabilized on alpha blocker therapy before the phosphodiesterase type-5 inhibitor is started at a low dose and adjusted according to response.

Drugs that inhibit the CYP450 isoenzyme CYP3A4, such as cimetidine, delavirdine, erythromycin, itraconazole, and ketoconazole, may reduce the clearance of phosphodiesterase type-5 inhibitors, necessitating a reduction in dosage.

Plasma concentrations of phosphodiesterase type-5 inhibitors are significantly increased by HIV-protease inhibitors, and particularly so by ritonavir-boosted regimens. Such combinations should not be given unless absolutely essential. Grapefruit juice should be avoided with Sildenafil 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. Bosenfan also reduces exposure to Sildenafil.

Pregnancy

Pregnancy Category B. There are no adequate and well-controlled studies of Sildenafil in pregnant women.

Lactation

There are no adequate and well controlled studies in pregnant women.

The evaluation or erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. Before prescribing Sildenafil Citrate, it is important to note the following:

Caution is advised when Phosphodiesterase Type 5 (PDE5) inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including Sildenafil Citrate and alpha-adrenergic blocking agents are moth vasodilators with blood pressure lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated.

Consideration should be given to the following:

Patients should be stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest dose. In those patients already taking an optimized dose of a PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure when taking a PDE5 inhibitor.

Safety of combined use of PDE5 inhibitors and alpha-blocker may be affected by other variables, including intravascular volume depletion and other anti-hypertensive drugs. Sildenafil citrate has systemic vasodilatory properties and may augment the blood pressure lowering effect of other anti-hypertensive medications.

The safety of Sildenafil Citrate is unknown in patients with bleeding disorders and patients with active peptic ulceration. Sildenafil Citrate 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 anemia, multiple myeloma, or leukemia).

The safety and efficacy of combinations of Sildenafil Citrate with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.

In humans, Sildenafil Citrate has no effect on bleeding time when taken alone or with aspirin. In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). The combination of heparin and Sildenafil Citrate had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans.

Pharmacotherapeutic group: Drugs used in erectile dysfunction

Sildenafil is an oral therapy for erectile dysfunction. In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis.

The physiological mechanism responsible for erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activated the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.

Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP. Sildenafil has a peripheral site of action on erections. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by Sildenafil results in increased corpus cavernosum levels of cGMP. Therefore sexual stimulation is required in order or Sildenafil to produce its intended beneficial pharmacological effects.