4 CONTRAINDICATIONS

In the clinical trial no greater efficacy was achieved with the use of higher doses. Treatment with doses higher than 20 mg three times a day is not recommended. Tap the bottle to release the powder. Accurately measure out 60 mL of water and pour the water into the bottle. Accurately measure out another 30 mL of water and add this to the bottle.

• Sildenafil syrup is sometimes used in pediatric cases, off-label.
• Off-label use in children requires careful dosage adjustment.
• Lack of standardization makes typical dosing guidelines difficult.
• Pharmacokinetics in syrup form are less well-studied.
• Always seek professional medical advice before use.

Press the bottle adaptor into the neck of the bottle (as shown on Figure 5, below). 3 DOSAGE FORMS AND STRENGTHS Sildenafil for Oral SuspensionWhite to off-white powders containing 1.57 g of sildenafil citrate (equivalent to 1.12 g of sildenafil) in a bottle intended for reconstitution. A 2 mL oral syringe (with 0.5 mL and 2 mL dose markings) and a press-in bottle adaptor are also provided. White to off-white powders containing 1.57 g of sildenafil citrate (equivalent to 1.12 g of sildenafil) in a bottle intended for reconstitution.

4 CONTRAINDICATIONS Sildenafil for Oral Suspension is contraindicated in patients with:Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.2)].Concomitant use of riociguat, a guanylate cyclase stimulator.

• Sildenafil can cause visual disturbances like blurred vision.
• Alcohol consumption may increase side effects when using sildenafil.
• The syrup should be stored at room temperature away from light.
• Patients should avoid heavy meals before taking sildenafil.
• Regular monitoring is recommended for long-term use.

PDE-5 inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.Known hypersensitivity to sildenafil or any component of the tablet, injection, or oral suspension. Sildenafil for Oral Suspension is contraindicated in patients with: Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.2)]. PDE-5 inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat. 5 WARNINGS AND PRECAUTIONS 5.1 Mortality with Pediatric UseIn a long-term trial in pediatric patients with PAH, an increase in mortality with increasing Sildenafil for Oral Suspension dose was observed.

4 CONTRAINDICATIONS

Physicians should also discuss the increased risk of NAION with patients who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators, such as PDE-5 inhibitors. Deaths were first observed after about 1 year and causes of death were typical of patients with PAH. Use of Sildenafil for Oral Suspension, particularly chronic use, is not recommended in children [see Use in Specific Populations (8.4)].5.2 HypotensionSildenafil has vasodilatory properties, resulting in mild and transient decreases in blood pressure. Before prescribing Sildenafil for Oral Suspension, carefully consider whether patients with certain underlying conditions could be adversely affected by such vasodilatory effects (e.g., patients on antihypertensive therapy or with resting hypotension [BP liquid sildenafil citrate less than 90/50], fluid depletion, severe left ventricular outflow obstruction, or autonomic dysfunction). Monitor blood pressure when co-administering blood pressure lowering drugs with Sildenafil for Oral Suspension.5.3 Worsening Pulmonary Vascular Occlusive DiseasePulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD).

Since there are no clinical data on administration of Sildenafil for Oral Suspension to patients with veno-occlusive disease, administration of Sildenafil for Oral Suspension to such patients is not recommended. Should signs of pulmonary edema occur when Sildenafil for Oral Suspension is administered, consider the possibility of associated PVOD.5.4 EpistaxisThe incidence of epistaxis was 13% in patients taking Sildenafil with PAH secondary to CTD. The incidence of epistaxis was also higher in Sildenafil for Oral Suspension-treated patients with a concomitant oral vitamin K antagonist (9% versus 2% in those not treated with concomitant vitamin K antagonist).The safety of Sildenafil for Oral Suspension is unknown in patients with bleeding disorders or active peptic ulceration.5.5 Visual LossWhen used to treat erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE-5) inhibitors, including sildenafil.

• The shelf life of sildenafil syrup depends on formulation and storage.
• Expiry dates should always be checked before use.
• Improper storage can lead to degradation of active ingredients.
• The liquid form allows for precise dose adjustments.
• Careful titration is essential to avoid overdose risks.

Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. Based on published literature, the annual incidence of NAION is 2.5–11.8 cases per 100,000 males aged ≥50 per year in the general population.An observational case-crossover study evaluated the risk of NAION when PDE-5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE-5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34).

What should I know about storage and disposal of this medication?

In the clinical trial no greater efficacy was achieved with the use of higher doses. Treatment with doses higher than 20 mg three times a day is not recommended. Tap the bottle to release the powder. Accurately measure out 60 mL of water and pour the water into the bottle. Accurately measure out another 30 mL of water and add this to the bottle.

Indications and Usage for Sildenafil Oral Suspension

Press the bottle adaptor into the neck of the bottle (as shown on Figure 5, below). 3 DOSAGE FORMS AND STRENGTHS Sildenafil for Oral SuspensionWhite to off-white powders containing 1.57 g of sildenafil citrate (equivalent to 1.12 g of sildenafil) in a bottle intended for reconstitution. A 2 mL oral syringe (with 0.5 mL and 2 mL dose markings) and a press-in bottle adaptor are also provided. White to off-white powders containing 1.57 g of sildenafil citrate (equivalent to 1.12 g of sildenafil) in a bottle intended for reconstitution. 4 CONTRAINDICATIONS Sildenafil for Oral Suspension is contraindicated in patients with:Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.2)].Concomitant use of riociguat, a guanylate cyclase stimulator.

Raynaud's phenomenon

PDE-5 inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.Known hypersensitivity to sildenafil or any component of the tablet, injection, or oral suspension. Sildenafil for Oral Suspension is contraindicated in patients with: Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.2)]. PDE-5 inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat. 5 WARNINGS AND PRECAUTIONS 5.1 Mortality with Pediatric UseIn a long-term trial in pediatric patients with PAH, an increase in mortality with increasing Sildenafil for Oral Suspension dose was observed. Deaths were first observed after about 1 year and causes of death were typical of patients with PAH. A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies.Neither the rare postmarketing reports, nor the association of PDE-5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE-5 inhibitor use and NAION [see Adverse Reactions (6.2].Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking PDE-5 inhibitors, including Sildenafil for Oral Suspension.

How is this medicine (Sildenafil Oral Suspension) best taken?

Inform patients taking Sildenafil for Oral Suspension not to take VIAGRA or other PDE-5 inhibitors.5.8 PriapismUse Sildenafil for Oral Suspension with caution in patients with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease) or in patients who have conditions, which may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia). If priapism (painful erection greater than 6 hours in duration) is not treated immediately, penile tissue damage and permanent loss of potency could result.5.9 Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell AnemiaIn a small, prematurely terminated study of patients with pulmonary hypertension (PH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported by patients who received Sildenafil for Oral Suspension than by those randomized to placebo. The effectiveness and safety of Sildenafil for Oral Suspension in the treatment of PAH secondary to sickle cell anemia has not been established. In a long-term trial in pediatric patients with PAH, an increase in chew sildenafil mortality with increasing Sildenafil for Oral Suspension dose was observed. Use of Sildenafil for Oral Suspension, particularly chronic use, is not recommended in children [see Use in Specific Populations (8.4)].

Incidence not known

Monitor blood pressure when co-administering blood pressure lowering drugs with Sildenafil for Oral Suspension. Should signs of pulmonary edema occur when Sildenafil for Oral Suspension is administered, consider the possibility of associated PVOD. The incidence of epistaxis was also higher in Sildenafil for Oral Suspension-treated patients with a concomitant oral vitamin K antagonist (9% versus 2% in those not treated with concomitant vitamin K antagonist). The safety of Sildenafil for Oral Suspension is unknown in patients with bleeding disorders or active peptic ulceration. When used to treat erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE-5) inhibitors, including sildenafil.

5.6 Combination with Other PDE-5 Inhibitors

Based on published literature, the annual incidence of NAION is 2.5–11.8 cases per 100,000 males aged ≥50 per year in the general population. An observational case-crossover study evaluated the risk of NAION when PDE-5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE-5 inhibitor use in a prior time period. Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. Neither the rare postmarketing reports, nor the association of PDE-5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE-5 inhibitor use and NAION [see Adverse Reactions (6.2]. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking PDE-5 inhibitors, including Sildenafil for Oral Suspension. Physicians should also discuss the increased risk of NAION with patients who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators, such as PDE-5 inhibitors.There are no controlled clinical data on the safety or efficacy of Sildenafil for Oral Suspension in patients with retinitis pigmentosa, a minority whom have genetic disorders of retinal phosphodiesterases. Prescribe Sildenafil for Oral Suspension with caution in these patients.5.6 Hearing LossCases of sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, have been reported in temporal association with the use of PDE-5 inhibitors, including Sildenafil. It is not possible to determine whether these reported events are related directly to the use of Sildenafil for Oral Suspension, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors.Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking PDE-5 inhibitors, including Sildenafil for Oral Suspension.5.7 Combination with other PDE-5 inhibitorsSildenafil is also marketed as VIAGRA®. The safety and efficacy of combinations of Sildenafil for Oral Suspension with VIAGRA or other PDE-5 inhibitors have not been studied. Inform patients taking Sildenafil for Oral Suspension not to take VIAGRA or other PDE-5 inhibitors.5.8 PriapismUse Sildenafil for Oral Suspension with caution in patients with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease) or in patients who have conditions, which may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia). If priapism (painful erection greater than 6 hours in duration) is not treated immediately, penile tissue damage and permanent loss of potency could result.5.9 Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell AnemiaIn a small, prematurely terminated study of patients with pulmonary hypertension (PH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported by patients who received Sildenafil for Oral Suspension than by those randomized to placebo. The effectiveness and safety of Sildenafil for Oral Suspension in the treatment of PAH secondary to sickle cell anemia has not been established. In a long-term trial in pediatric patients with PAH, an increase in chew sildenafil mortality with increasing Sildenafil for Oral Suspension dose was observed. Use of Sildenafil for Oral Suspension, particularly chronic use, is not recommended in children [see Use in Specific Populations (8.4)]. Monitor blood pressure when co-administering blood pressure lowering drugs with Sildenafil for Oral Suspension. Should signs of pulmonary edema occur when Sildenafil for Oral Suspension is administered, consider the possibility of associated PVOD. The incidence of epistaxis was also higher in Sildenafil for Oral Suspension-treated patients with a concomitant oral vitamin K antagonist (9% versus 2% in those not treated with concomitant vitamin K antagonist).

Related/similar drugs

Use of Sildenafil for Oral Suspension, particularly chronic use, is not recommended in children [see Use in Specific Populations (8.4)].5.2 HypotensionSildenafil has vasodilatory properties, resulting in mild and transient decreases in blood pressure. Before prescribing Sildenafil for Oral Suspension, carefully consider whether patients with certain underlying conditions could be adversely affected by such vasodilatory effects (e.g., patients on antihypertensive therapy or with resting hypotension [BP liquid sildenafil citrate less than 90/50], fluid depletion, severe left ventricular outflow obstruction, or autonomic dysfunction). Monitor blood pressure when co-administering blood pressure lowering drugs with Sildenafil for Oral Suspension.5.3 Worsening Pulmonary Vascular Occlusive DiseasePulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Since there are no clinical data on administration of Sildenafil for Oral Suspension to patients with veno-occlusive disease, administration of Sildenafil for Oral Suspension to such patients is not recommended. Should signs of pulmonary edema occur when Sildenafil for Oral Suspension is administered, consider the possibility of associated PVOD.5.4 EpistaxisThe incidence of epistaxis was 13% in patients taking Sildenafil with PAH secondary to CTD.

Limitation of Warranty & Liability

The incidence of epistaxis was also higher in Sildenafil for Oral Suspension-treated patients with a concomitant oral vitamin K antagonist (9% versus 2% in those not treated with concomitant vitamin K antagonist).The safety of Sildenafil for Oral Suspension is unknown in patients with bleeding disorders or active peptic ulceration.5.5 Visual LossWhen used to treat erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE-5) inhibitors, including sildenafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. Based on published literature, the annual incidence of NAION is 2.5–11.8 cases per 100,000 males aged ≥50 per year in the general population.An observational case-crossover study evaluated the risk of NAION when PDE-5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE-5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20).

What should I know about sildenafil before taking it?

Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies.Neither the rare postmarketing reports, nor the association of PDE-5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE-5 inhibitor use and NAION [see Adverse Reactions (6.2].Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking PDE-5 inhibitors, including Sildenafil for Oral Suspension. Physicians should also discuss the increased risk of NAION with patients who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators, such as PDE-5 inhibitors.There are no controlled clinical data on the safety or efficacy of Sildenafil for Oral Suspension in patients with retinitis pigmentosa, a minority whom have genetic disorders of retinal phosphodiesterases. Prescribe Sildenafil for Oral Suspension with caution in these patients.5.6 Hearing LossCases of sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, have been reported in temporal association with the use of PDE-5 inhibitors, including Sildenafil. It is not possible to determine whether these reported events are related directly to the use of Sildenafil for Oral Suspension, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors.Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking PDE-5 inhibitors, including Sildenafil for Oral Suspension.5.7 Combination with other PDE-5 inhibitorsSildenafil is also marketed as VIAGRA®. The safety and efficacy of combinations of Sildenafil for Oral Suspension with VIAGRA or other PDE-5 inhibitors have not been studied. The safety of Sildenafil for Oral Suspension is unknown in patients with bleeding disorders or active peptic ulceration. When used to treat erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE-5) inhibitors, including sildenafil. Based on published literature, the annual incidence of NAION is 2.5–11.8 cases per 100,000 males aged ≥50 per year in the general population. An observational case-crossover study evaluated the risk of NAION when PDE-5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE-5 inhibitor use in a prior time period. Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. Neither the rare postmarketing reports, nor the association of PDE-5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE-5 inhibitor use and NAION [see Adverse Reactions (6.2]. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking PDE-5 inhibitors, including Sildenafil for Oral Suspension. Physicians should also discuss the increased risk of NAION with patients who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators, such as PDE-5 inhibitors.

What special dietary instructions should I follow?