Degra

Adults

Treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease.

Paediatric population

Treatment of paediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension. Efficacy in terms of improvement of exercise capacity or pulmonary haemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease.

Degra is indicated in adult men with erectile dysfunction, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance.

In order for Degra to be effective, sexual stimulation is required.

Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension. In case of clinical deterioration in spite of Degra treatment, alternative therapies should be considered.

Posology

Adults

The recommended dose is 20 mg three times a day (TID). Physicians should advise patients who forget to take Degra to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.

Paediatric population (1 year to 17 years)

For paediatric patients aged 1 year to 17 years old, the recommended dose in patients ≤ 20 kg is 10 mg (1 ml of reconstituted suspension) three times a day and for patients > 20 kg is 20 mg (2 ml of reconstituted suspension) three times a day.1).

Patients using other medicinal products

In general, any dose adjustment should be administered only after a careful benefit-risk assessment. Dose adjustments for sildenafil may be required when co-administered with CYP3A4 inducers.

Special populations

Elderly (> 65 years)

Dose adjustments are not required in elderly patients. Clinical efficacy as measured by 6-minute walk distance could be less in elderly patients.

Renal impairment

Initial dose adjustments are not required in patients with renal impairment, including severe renal impairment (creatinine clearance < 30 ml/min). A downward dose adjustment to 20 mg twice daily should be considered after a careful benefit-risk assessment only if therapy is not well-tolerated.

Hepatic impairment

Initial dose adjustments are not required in patients with hepatic impairment (Child-Pugh class A and B). A downward dose adjustment to 20 mg twice daily should be considered after a careful benefit-risk assessment only if therapy is not well-tolerated.

Degra is contraindicated in patients with severe hepatic impairment (Child-Pugh class C),.

Paediatric population

The safety and efficacy of Degra in children below 1 year of age has not been established. No data are available.

Discontinuation of treatment

Limited data suggest that the abrupt discontinuation of Degra is not associated with rebound worsening of pulmonary arterial hypertension. However to avoid the possible occurrence of sudden clinical deterioration during withdrawal, a gradual dose reduction should be considered. Intensified monitoring is recommended during the discontinuation period.

Method of administration

Degra powder for oral suspension is for oral use only. The constituted oral suspension (a white, grape flavoured oral suspension) should be taken approximately 6 to 8 hours apart with or without food.

Before withdrawing the required dose, shake the bottle vigorously for a minimum of 10 seconds.

Posology

Use in adults

The recommended dose is 50 mg taken as needed approximately one hour before sexual activity. Based on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once per day. If Degra is taken with food, the onset of activity may be delayed compared to the fasted state.

Special populations

Elderly

Dosage adjustments are not required in elderly patients (> 65 years old).

Renal impairment

The dosing recommendations described in “Use in adults” apply to patients with mild to moderate renal impairment (creatinine clearance = 30-80 mL/min).

Since sildenafil clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 mL/min) a 25 mg dose should be considered. Based on efficacy and tolerability, the dose may be increased step-wise to 50 mg up to 100 mg as necessary.

Hepatic impairment

Since sildenafil clearance is reduced in patients with hepatic impairment (e.g. cirrhosis) a 25 mg dose should be considered. Based on efficacy and tolerability, the dose may be increased step-wise to 50 mg up to 100 mg as necessary.

Paediatric population

Degra is not indicated for individuals 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 25 mg should be considered in patients receiving concomitant treatment with CYP3A4 inhibitors.

In order to minimise the potential of developing postural hypotension in patients receiving alpha-blocker treatment patients should be stabilised on alpha-blocker therapy prior to initiating sildenafil treatment. In addition, initiation of sildenafil at a dose of 25 mg should be considered.

Method of administration

For oral use.

Co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form due to the hypotensive effects of nitrates.

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.

Combination with the most potent of the CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir).

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 safety of sildenafil has not been studied in the following sub-groups of patients and its use is therefore contraindicated:

Severe hepatic impairment,

Recent history of stroke or myocardial infarction,

Severe hypotension (blood pressure < 90/50 mmHg) at initiation.

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 nitrite) or nitrates in any form is therefore 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.

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).

Degra 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 safety of sildenafil has not been studied in the following sub-groups 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 pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).