Sildazen

/ Taro International Ltd

Use in adults: the recommended dose is 2 mL (4 actuations) taken as needed, approximately one hour before sexual activity. Based on efficacy and tolerability, the dose may be increased to 4 mL (8 actuations), or decreased to 1 mL (2 actuations). The maximum recommended dose is 4 mL (8 actuations). The maximum recommended dosing frequency is once per day.
If this product is taken with food, the onset of its pharmacological activity may be delayed compared to the fasted state.
Special populations
Renal impairment
Sildenafil clearance is reduced in patients with severe renal impairment (creatinine clearance <30 mL/min) a 25 mg dose (2 actuations) should be considered for these patients. Based on efficacy and tolerability, the dose may be increased step-wise to 50 mg.
Hepatic impairment
Since Sildenafil clearance is reduced in patients with hepatic impairment (e.g. cirrhosis) a 25 mg dose (2 actuations) should be considered for these patients. Based on efficacy and tolerability, the dose may be increased step-wise to 50 mg.
Paediatric population
This product is not indicated for children and adolescents below 18 years of age.
Use in patients taking other medicinal products
With the exception of ritonavir, for which co-administration with Sildenafil is not advised, a starting dose of 1 mL (2 actuations) equivalent to 25 mg should be considered in patients receiving concomitant treatment with CYP3A4 inhibitors.
In order to minimise the potential for developing postural hypotension in patients receiving alpha-blocker treatment, patients should be stabilised on alpha-blocker therapy prior to initiating Sildenafil administration. In addition, initiation of Sildenafil treatment at a dose of 1 mL (2 actuations) should be considered.

For adult men with erectile dysfunction

* Hypersensitivity to the active substance or to any of the excipients.
* The co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form is contraindicated.
* The co-administration of PDE5 inhibitors, including Sildenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension.
* 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 heart failure).
* Patients who have loss of vision in one eye due to non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether or not this episode was associated with previous PDE5 inhibitor exposure.
* Sub-groups of patients: 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 pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

Cardiovascular risk factors: Prior to initiating any treatment for erectile dysfunction, the physician should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Sildenafil has vasodilator properties, resulting in mild and transient decreases in blood pressure. Prior to prescribing Sildenafil, the physician should carefully consider whether their patients with certain underlying conditions could be adversely affected by such vasodilator effects, especially in combination with sexual activity. Patients with increased susceptibility to vasodilators include those with left ventricular outflow obstruction (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy) or those with the rare syndrome of multiple system atrophy manifesting as severely impaired autonomic control of blood pressure. Sildenafil potentiates the hypotensive effect of nitrates.
Priapism: 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 with conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia). Prolonged erections and priapism have been reported with Sildenafil in post-marketing experience. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.
Concomitant use with other PDE5 inhibitors or other treatments for erectile dysfunction: The safety and efficacy of combinations of Sildenafil with other PDE5 inhibitors, have not been studied. Therefore, the use of such combinations is not recommended.
Effects on vision: Cases of visual defects have been reported spontaneously in connection with the intake of S
Sildenafil and other PDE5 inhibitors. Cases of non-arteritic anterior ischaemic optic neuropathy, a rare condition, have been reported spontaneously and in an observational study in connection with the intake of Sildenafil and other PDE5 inhibitors. Patients should be advised that, in the event of any sudden visual defect, they should stop taking Sildenafil and consult a physician immediately.
Concomitant use with ritonavir: Co-administration of Sildenafil with ritonavir is not advised.
Concomitant use with alpha-blockers: Caution is advised when Sildenafil is administered to patients taking an alpha-blocker, as the co-administration of both drugs may lead to symptomatic hypotension in a small number of more susceptible patients. This is most likely to occur within 4 hours after taking Sildenafil. In order to minimise the potential for developing postural hypotension, patients receiving alpha-blocker treatment should be haemodynamically stable on alpha-blocker therapy prior to initiating Sildenafil treatment. Furthermore, initiation of Sildenafil treatment at a dose of 25 mg (two actuations) should be considered. In addition, physicians should advise their patients what to do in the event of postural hypotensive symptoms.
Effects on bleeding: Studies with human platelets indicate that Sildenafil potentiates the antiaggregatory effect of sodium nitroprusside in vitro. There are no safety data on the administration of Sildenafil to patients with bleeding disorders or active peptic ulcer. Therefore, Sildenafil should be administered to these patients only after benefit-risk assessment.
Use in women
Sildenafil is not indicated for use by women.
See prescribing information for full details

Very common: Headache
Common: dizziness, visual colour distortions, visual disturbance, blurred vision, flushing, hot flush, nasal congestion, nausea, dyspepsia
See prescribing information for full details

Effects of other medicinal products on Sildenafil
* Sildenafil metabolism is mediated primarily by the cytochrome P450 (CYP) isoforms 3A4. Therefore, inhibitors of these isoenzymes may reduce Sildenafil clearance and inducers of these isoenzymes may increase Sildenafil clearance. A reduction in Sildenafil clearance when co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although no increased incidence of adverse events was observed in these patients, when Sildenafil is administered concomitantly with CYP3A4 inhibitors, a starting dose of 25 mg (two actuations) should be considered.
* Co-administration of Sildenafil with ritonavir is not advised, and the maximum dose of Sildenafil should under no circumstances exceed 25 mg (two actuations) in 48 hours.
* Grapefruit juice is a weak inhibitor of cytochrome CYP3A4 gut wall metabolism and may give rise to modest increases in plasma levels of Sildenafil.
Effects of Sildenafil on other medicinal products
* Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. It is unlikely that Sildenafil will alter the clearance of substrates of these isoenzymes.
* Consistent with its known effects on the nitric oxide/cGMP pathway, Sildenafil was shown to potentiate the hypotensive effects of nitrates. Its co-administration with nitric oxide donors or nitrates is therefore contraindicated
* Concomitant administration of Sildenafil to patients taking alpha-blocker therapy may lead to symptomatic hypotension in a small number of more susceptible patients. This is most likely to occur within 4 hours of taking Sildenafil.
* The addition of a single dose of Sildenafil to sacubitril/valsartan at steady state in patients with hypertension was associated with a significantly greater reduction in blood pressure compared to the administration of sacubitril/valsartan alone. Therefore, caution should be exercised when initiating Sildenafil treatment in patients taking sacubitril/valsartan.
See prescribing information for full details.

Sildenafil is not indicated for use by women.

In studies in healthy volunteers with single doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased. Doses of 200 mg did not result in increased efficacy but the incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion and altered vision) was increased.
In cases of overdose, standard supportive measures should be adopted. Renal dialysis is not expected to accelerate clearance of the drug as Sildenafil is highly bound to plasma proteins and not eliminated in the urine.