Granpidam 20 mg film-coated tablets
Each film-coated tablet contains 20 mg of sildenafil (as citrate).
Excipient(s) with known effect
Each tablet also contains 0.2 mg of lactose (as monohydrate).
For the full list of excipients, see section 6.1.
Film-coated tablet (tablet).
White to off white, round shaped, approximately 6.6 mm in diameter, biconvex, film-coated tablets, debossed with '20' on one side and plain on other side.
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 (see section 5.1).
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 Granpidam 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 Granpidam 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 three times a day and for patients >20 kg is 20 mg three times a day. Higher than recommended doses should not be used in paediatric patients with PAH (see also sections 4.4 and 5.1). The 20 mg tablet should not be used in cases where 10 mg TID should be administered in younger patients. Other pharmaceutical forms are available for administration to patients ≤20 kg and other younger patients who are not able to swallow tablets.
Patients using other medicinal products
In general, any dose adjustment should be administered only after a careful benefit-risk assessment. A downward dose adjustment to 20 mg twice daily should be considered when sildenafil is co-administered to patients already receiving CYP3A4 inhibitors like erythromycin or saquinavir. A downward dose adjustment to 20 mg once daily is recommended in case of co-administration with more potent CYP3A4 inhibitors clarithromycin, telithromycin and nefazodone. For the use of sildenafil with the most potent CYP3A4 inhibitors, see section 4.3. Dose adjustments for sildenafil may be required when co-administered with CYP3A4 inducers (see section 4.5).
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.
Granpidam is contraindicated in patients with severe hepatic impairment (Child-Pugh class C) (see section 4.3).
Paediatric population
The safety and efficacy of sildenafil in children below 1 year of age has not been established. No data are available.
Discontinuation of treatment
Limited data suggests that the abrupt discontinuation of sildenafil 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
Granpidam is for oral use only. Tablets should be taken approximately 6 to 8 hours apart with or without food.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form due to the hypotensive effects of nitrates (see section 5.1).
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 (see section 4.5).
Combination with the most potent of the CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir) (see section 4.5).
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 (see section 4.4).
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.
The efficacy of sildenafil has not been established in patients with severe pulmonary arterial hypertension (functional class IV). If the clinical situation deteriorates, therapies that are recommended at the severe stage of the disease (e.g. epoprostenol) should be considered (see section 4.2). The benefit-risk balance of sildenafil has not been established in patients assessed to be at WHO functional class I pulmonary arterial hypertension.
Studies with sildenafil have been performed in forms of pulmonary arterial hypertension related to primary (idiopathic), connective tissue disease associated or congenital heart disease associated forms of PAH (see section 5.1). The use of sildenafil in other forms of PAH is not recommended.
In the long term paediatric extension study, an increase in deaths was observed in patients administered doses higher than the recommended dose. Therefore, doses higher than the recommended doses should not be used in paediatric patients with PAH (see also sections 4.2 and 5.1).
Retinitis pigmentosa
The safety of sildenafil has not been studied in patients with known hereditary degenerative retinal disorders such as retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases) and therefore its use is not recommended.
Vasodilatory action
When prescribing sildenafil, physicians should carefully consider whether patients with certain underlying conditions could be adversely affected by sildenafil's mild to moderate vasodilatory effects, for example patients with hypotension, patients with fluid depletion, severe left ventricular outflow obstruction or autonomic dysfunction (see section 4.4).
Cardiovascular risk factors
In post-marketing experience with sildenafil for male erectile dysfunction, serious cardiovascular events, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular haemorrhage, transient ischaemic attack, hypertension and hypotension have been reported in temporal association with the use of sildenafil. Most, but not all, of these patients had pre-existing cardiovascular risk factors. Many events were reported to occur during or shortly after sexual intercourse and a few were reported to occur shortly after the
