Presentation and Status in Health Basket
Film Coated Tablets
90 x 20 mg
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 Revatio treatment, alternative therapies should be considered.
Adults: The recommended dose is 20 mg three times a day (TID). Physicians should advise patients who forget to take Revatio 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.
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. Dose adjustments for sildenafil may be required when co-administered with CYP3A4 inducers.
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. Revatio is contraindicated in patients with severe hepatic impairment (Child-Pugh class C).
Discontinuation of treatment: Limited data suggest that the abrupt discontinuation of Revatio 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: Revatio is for oral use only. Tablets should be taken approximately 6 to 8 hours apart with or without food.
For adults > 18 years: Treatment of primary pulmonary hypertension (PPH) pulmonary hypertension (PH) associated with connective tissue disease (CTD) or PH following surgical repair at least 5 years previously of atrial septal defect (ASD) ventricular septal defect (VSD) patent ductus arteriosus (PDA) or aorto-pulmonary window.
Hypersensitivity to the active substance or to any of the excipients. 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. 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 Revatio 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 (eg, 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.
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 preexisting 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). 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 Revatio 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 coadministration 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 thesepatients 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.
Galactose intolerance: Lactose monohydrate is present in the tablet film coat. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take thismedicine.
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.
The most commonly reported adverse reactions that occurred (greater or equal to 10 %) on Revatio compared to placebo were headache, flushing, dyspepsia, diarrhoea and limb pain.
For full details see prescribing information.
Effects of other medicinal products on sildenafil
In vitro studies: Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.
In vivo studies: Co-administration of oral sildenafil and intravenous epoprostenol has been evaluated. The efficacy and safety of sildenafil co-administered with other treatments for pulmonary arterial hypertension (e.g., ambrisentan ,iloprost) has not been studied in controlled clinical trials. Therefore, caution is recommended in case of co-administration.
The safety and efficacy of sildenafil when co-administered with other PDE5 inhibitors has not been studied in pulmonary arterial hypertension patients.
Effects of sildenafil on other medicinal products
In vitro studies: Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 μM).
There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.
In vivo studies: No significant interactions were shown when sildenafil (50 mg) was co-administered with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9. Sildenafil had no significant effect on atorvastatin exposure (AUC increased 11 %), suggesting that sildenafil does not have a clinically relevant effect on CYP3A4.
For full details see prescribing information.
Pregnancy and Lactation
Pregnancy: There are no data from the use of sildenafil in pregnant women. Due to lack of data, Revatio should not be used in pregnant women unless strictly necessary.
Breast feeding: There are no adequate and well controlled studies in lactating women. Data from one lactating woman indicate that sildenafil and its active metabolite N-desmethylsildenafil are excreted into breast milk at very low levels. No clinical data are available regarding adverse events in breast-fed infants, but amounts ingested would not be expected to cause any adverse effects. Prescribers should carefully assess the mother’s clinical need for sildenafil and any potential adverse effects on the breast-fed child.
For full details see prescribing information.
In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased. At single doses of 200 mg 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 as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.
Storage: Store below 30°C, in a dry place.