Sildenafil Oral Suspension Abbreviated Prescribing Information

Name of the medicinal product: Sildenafil 10 mg/ml Oral suspension. Qualitative and quantitative composition: Each ml of the oral suspension contains 10 mg of sildenafil (as citrate). Pharmaceutical form: Oral suspension. White to off white oral suspension. Therapeutic indications: 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. Posology and method of administration: 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 Sildenafil 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 Sildenafil 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. 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. 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. Sildenafil is contraindicated in patients with severe hepatic impairment (Child-Pugh class C). 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 suggest 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 Sildenafil Oral suspension is for oral use only. Doses should be taken approximately 6 to 8 hours apart with or without food. Shake well before use. For instructions for use of the medicinal product before administration, see section 6.6 of the SmPC. Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC. 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 (e.g., 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 (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. Special warnings and precautions for use: 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. 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. 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. 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. 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 use of sildenafil without sexual activity. It is not possible to determine whether these events are related directly to these factors or to other factors. Priapism Sildenafil 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 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. Vaso-occlusive crises in patients with sickle cell anaemia Sildenafil should not be used in patients with pulmonary hypertension secondary to sickle cell anaemia. In a clinical study events of vaso-occlusive crises requiring hospitalisation were reported more commonly by patients receiving Sildenafil than those receiving placebo leading to the premature termination of this study. Visual events Cases of visual defects have been reported spontaneously in connection with the intake of 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. In the event of any sudden visual defect, the treatment should be stopped immediately and alternative treatment should be considered. Alpha-blockers Caution is advised when sildenafil is administered to patients taking an alpha-blocker as the co-administration may lead to symptomatic hypotension in susceptible individuals. In order to minimise the potential for developing postural hypotension, patients should be haemodynamically stable on alpha-blocker therapy prior to initiating sildenafil treatment. Physicians should advise patients what to do in the event of postural hypotensive symptoms. Bleeding disorders Studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside in vitro. There is no safety information on the administration of sildenafil to patients with bleeding disorders or active peptic ulceration. Therefore sildenafil should be administered to these patients only after careful benefit-risk assessment. Vitamin K antagonists In pulmonary arterial hypertension patients, there may be a potential for increased risk of bleeding when sildenafil is initiated in patients already using a Vitamin K antagonist, particularly in patients with pulmonary arterial hypertension secondary to connective tissue disease. Veno-occlusive disease No data are available with sildenafil in patients with pulmonary hypertension associated with pulmonary veno-occlusive disease. However, cases of life-threatening pulmonary oedema have been reported with vasodilators (mainly prostacyclin) when used in those patients. Consequently, should signs of pulmonary oedema occur when sildenafil is administered in patients with pulmonary hypertension, the possibility of associated veno-occlusive disease should be considered. Use of sildenafil with bosentan The efficacy of sildenafil in patients already on bosentan therapy has not been conclusively demonstrated. Concomitant use with other PDE5 inhibitors The safety and efficacy of sildenafil when co-administered with other PDE5 inhibitor products, including Viagra, has not been studied in PAH patients and such concomitant use is not recommended. Excipient warnings  Sildenafil Oral suspension contains sodium benzoate: Sodium benzoate (E211): This medicine contains 2.0 mg sodium benzoate  in each ml. This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’. Undesirable effects (summary only, see SmPC for full details): The following undesirable effects are very common (≥1/10): headache, flushing, diarrhoea, dyspepsia, pain in extremity. The following undesirable effects are common (≥1/100, < 1/10): cellulitis, influenza, bronchitis, sinusitis, rhinitis, gastroenteritis, anaemia, fluid retention, insomnia, anxiety, migraine, tremor, paraesthesia, burning sensation, hypoaesthesia, retinal haemorrhage, visual impairment, vision blurred, photophobia, chromatopsia, cyanopsia, eye irritation, ocular hyperaemia, vertigo, epistaxis, cough, nasal congestion, gastritis, gastro-oesophageal reflux disease, haemorrhoids, abdominal distension, dry mouth, alopecia, erythema, night sweats, myalgia, backpain, pyrexia. The following undesirable effects are considered serious: retinal haemorrhage, visual impairment, non-arteritic anterior ischaemic optic neuropathy (NAION), retinal vascular occlusion, visual field defect, sudden hearing loss, haematuria, penile haemorrhage, haematospermia, priapism. Legal classification: POM (Prescription Only Medicine). Marketing authorisation holder: Rosemont Pharmaceuticals Ltd, Yorkdale Industrial Park, Braithwaite Street, Leeds, LS11 9XE, UK. Marketing authorisation number: PL 00427/0258. Date of text: January 2022. Cost: £186.75.