Sildenafil

Registered South African indications:

• Pulmonary arterial hypertension (PAH)
• Erectile dysfunction

Contraindications

South African recommendations

For the indication of pulmonary arterial hypertension (PAH)

• Hypersensitivity to the active substance or to any of the excipients
• Coadministration to patients who are concurrently using nitric oxide donors, organic nitrates or organic nitrites in any form either regularly or intermittently (medical practitioners should discuss with patients the contraindication of sildenafil with concurrent organic nitrates)
• The coadministration of PDE5 inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat
• Concomitant use of sildenafil with potent cytochrome P450 3A4 inhibitors e.g. ritonavir, erythromycin, saquinavir, ketoconazole and itraconazole
• Severe hepatic impairment
• Severe impairment of renal function (creatinine clearance <30ml/min)
• Patients with a systemic blood pressure of under 90/50mmHg

For the indication of erectile dysfunction

25mg, 50mg and 100mg tablets and film coated tablets

• Hypersensitivity to the active substance or to any of the excipients
• Coadministration to patients who are concurrently using nitric oxide donors, organic nitrates or organic nitrites in any form either regularly or intermittently (medical practitioners should discuss with patients the contraindication of sildenafil with concurrent organic nitrates)
• Concomitant use of sildenafil with potent cytochrome P450 3A4 inhibitors e.g. ritonavir, erythromycin, saquinavir, ketoconazole and itraconazole
• Sildenafil 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 coadministration of PDE5 inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat
• Severe hepatic impairment
• Severe impairment of renal function (creatinine clearance <30ml/min) not on haemodialysis or continuous ambulatory peritoneal dialysis

25mg, 50mg, and 100mg chewable tablets

• Hypersensitivity to the active substance or to any of the excipients
• Coadministration with nitric oxide donors (such as amyl nitrite), nitrites in any form either regularly or intermittently
• 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
• Sildenafil 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
• Severe hepatic impairment (e.g. cirrhosis)
• Severe impairment of renal function (creatinine clearance <30ml/min)
• Concomitant use of potent cytochrome P450 3A4 inhibitors (e.g. erythromycin, ritonavir, saquinavir, ketoconazole, itraconazole)

Recommendations in other jurisdictions

For the indication of pulmonary arterial hypertension (PAH)

• 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
• 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
• Severe hepatic impairment
• Recent history of stroke or myocardial infarction
• Severe hypotension (blood pressure<90/50mmHg) at initiation

For the indication of erectile dysfunction

• Hypersensitivity to the active substance or to any of the excipients
• Coadministration with nitric oxide donors (such as amyl nitrite) or nitrates in any form
• Coadministration of sildenafil with ritonavir (a highly potent P450 enzyme inhibitor)
• The co-administration of phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat
• Agents for the treatment of erectile dysfunction, including sildenafil, should not be used by those men for whom sexual activity may be inadvisable, and these patients should be referred to their doctor. This includes patients with severe cardiovascular disorders such as a recent (6 months) acute myocardial infarction (AMI) or stroke, unstable angina or severe cardiac failure
• Severe hepatic impairment
• Hypotension (blood pressure<90/50mmHg)
• Known hereditary degenerative retinal disorders such as retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases)
• Sildenafil 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
• Sildenafil should not be used in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease)
• Sildenafil is not indicated for use by women
• The product is not intended for men without erectile dysfunction
• This product is not intended for men under 18 years of age

Cautions

• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment (Erectile dysfunction) (South African recommendations)
• Renal impairment (Recommendations in other jurisdictions)
• Mild to moderate hepatic impairment (Erectile dysfunction) (South African recommendations)
• Mild to moderate hepatic impairment (Recommendations in other jurisdictions)
• Elderly
• Pulmonary arterial hypertension: functional class IV and class I
• Pulmonary arterial hypertension other than primary (idiopathic), or forms associated with connective tissue disease or congenital heart disease
• Retinitis pigmentosa
• Fluid depletion
• Severe left ventricular outflow obstruction
• Autonomic dysfunction
• Cardiovascular risk factors
• Anatomical deformities of penis
• Priapism or risk factors thereof
• Sickle cell anaemia
• Bleeding disorders
• Active peptic ulceration
• Pulmonary veno-occlusive disease
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab, fct, chu

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Pulmonary arterial hypertension (PAH)
- To improve exercise ability and to reduce mean pulmonary arterial pressure

• Oral (fct): 20mg, approximately 6-8hrly apart (three times a day) with or without food

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Efficacy of sildenafil film-coated tablets at a dose of 20mg three times a day has not been established in a sufficient number of patients beyond 12 weeks of treatment

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Erectile dysfunction

• Oral (tab, fct, chu): 50mg, taken as needed 1hr before sexual activity; Dose range: 25-100mg, based on efficacy and toleration; Max: 100mg/24hrs; Max frequency: Once per day

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Sildenafil is not an aphrodisiac

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Sildenafil chewable tablets should be chewed before swallowed

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If sildenafil chewable tablet is taken with food, the onset of activity may be delayed compared to the fasted state

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Indications and dosages registered in other jurisdictions

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)

• Oral (fct): 20mg, approximately 6-8hrly apart (three times a day) with or without food

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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

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Missed dose: Patients who forget to take sildenafil should be advised 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

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Dose adjustment should be considered when coadministration with CYP3A4 inhibitors and inducers

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Method of administration: Sildenafil is for oral use only

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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

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Erectile dysfunction

• Oral (tab, fct): 50mg, taken as needed 1hr before sexual activity; Dose range: 25-100mg, based on efficacy and tolerability; Max: 100mg/24hrs; Max frequency: Once per day

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In order for sildenafil to be effective, sexual stimulation is required

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If sildenafil is taken with food, the onset of activity may be delayed compared to the fasted state

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Patients should be advised that they may need to take sildenafil 50mg a number of times on different occasions (a maximum of one 50mg tablet per day), before they can achieve a penile erection satisfactory for sexual activity. If after several attempts on different dosing occasions patients are still not able to achieve a penile erection sufficient for satisfactory sexual activity, they should be advised to consult a doctor

Forms avail. in SA and covered in this monograph: tab, fct

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

• Not indicated for use in children below 18 years for erectile dysfunction
• Not recommended for children below 18 years for pulmonary arterial hypertension (PAH)

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Indications and dosages registered in other jurisdictions

Pulmonary arterial hypertension (PAH)
- Improvement of exercise capacity or pulmonary haemodynamics in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease

Younger than 1 year (and neonates)

• Not established for use

Between 1-17 years

• ≤20kg: Oral (fct): 10mg, approximately 6-8hrly apart (three times a day) with or without food
• >20kg: Oral (fct): 20mg, approximately 6-8hrly apart (three times a day) with or without food

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Outside its authorised indications, sildenafil should not be used in neonates with persistent pulmonary hypertension of the newborn as risks outweigh the benefits. The safety and efficacy of sildenafil in other conditions in children below 1 year of age has not been established. No data are available

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Higher than recommended doses should not be used in paediatric patients with PAH

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The 20mg tablet should not be used in cases where 10mg, 8hrly should be administered in younger patients. Other pharmaceutical forms are available in some jurisdictions for administration to patients ≤20kg and other younger patients who are not able to swallow tablets

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Method of administration: Sildenafil is for oral use only

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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

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Erectile dysfunction

• Contraindicated

Pregnancy

• Not indicated for use in women
• There are no data from the use of sildenafil in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy and embryonal/foetal development. Studies in animals have shown toxicity with respect to postnatal development. Due to lack of data, sildenafil should not be used in pregnant women unless strictly necessary

Breastfeeding

• Caution; not recommended
• There are no adequate and well-controlled studies in breastfeeding women
• It is not known whether sildenafil enters breast milk. Sildenafil should not be administered to breastfeeding mothers

Renal Impairment

South African recommendations

Pulmonary arterial hypertension

• Mild to moderate: No dose adjustment recommended
• Severe (CrCl<30ml/min): Contraindicated

Erectile dysfunction

• Mild to moderate: Caution; dose adjustment recommended
  A starting dose of 25mg should not be exceeded
• Severe (not on haemodialysis or continuous ambulatory peritoneal dialysis) (CrCl<30ml/min): Contraindicated

Recommendations in other jurisdictions

Pulmonary arterial hypertension

• Initial: No dose adjustment recommended
• Maintenance: Caution; dose adjustment recommended
  A downward dose adjustment to 20mg twice daily should be considered after a careful benefit-risk assessment only if therapy is not well tolerated

Erectile dysfunction

• Mild to moderate: No dose adjustment recommended
• Severe (CrCl<30ml/min): Caution; dose adjustment recommended
  Since sildenafil clearance is reduced in patients with severe renal impairment (CrCl<30ml/min) a 25mg dose should be considered. Based on efficacy and tolerability, the dose may be increased step-wise to 50mg up to 100mg as necessary

Hepatic Impairment 

South African recommendations

Pulmonary arterial hypertension

• Mild to moderate (Child-Pugh class A and B): No dose adjustment recommended
• Severe (Child-Pugh class C): Contraindicated

Erectile dysfunction

• Mild to moderate: Caution; dose adjustment recommended
  A starting dose of 25mg should not be exceeded
• Severe: Contraindicated

Recommendations in other jurisdictions

Pulmonary arterial hypertension

• Mild to moderate (Child-Pugh class A and B): Initial: No dose adjustment recommended
• Mild to moderate (Child-Pugh class A and B): Maintenance: Caution; dose adjustment recommended
  A downward dose adjustment to 20mg twice daily should be considered after a careful benefit-risk assessment only if therapy is not well-tolerated
• Severe (Child-Pugh class C): Contraindicated

Erectile dysfunction

• Mild to moderate (e.g. cirrhosis): Caution; dose adjustment recommended
  A 25mg dose should be considered. Based on efficacy and tolerability, the dose may be increased step-wise to 50mg up to 100mg as necessary
• Severe: Contraindicated

Elderly

• Caution; no dose adjustment recommended
  Use with high caution; Monitor blood pressure changes
  Start with lower dosage formulations (20-25mg); Max: 100mg/24hrs in divided doses
  Avoid chewable preparations

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Somnolence
• Hypoaesthesia
• Cerebrovascular accident
• Syncope
• Transient ischaemic attack
• Seizure
• Insomnia
• Anxiety
• Fatigue

Cardiovascular Disorders

• Palpitations
• Tachycardia
• Myocardial infarction
• Atrial fibrillation
• Ventricular arrhythmia
• Angina unstable
• Sudden cardiac death
• Flushing
• Hypotension

Respiratory Disorders

• Epistaxis
• Cough
• Nasal congestion
• Influenza
• Bronchitis
• Sinusitis
• Rhinitis

Gastrointestinal Disorders

• Gastroenteritis
• Dyspepsia
• Vomiting and nausea
• Dry mouth
• Glossitis

Genitourinary Disorders

• Haematuria
• Penile haemorrhage
• Haematospermia
• Priapism
• Increased erection 
• Urinary incontinence
• Nocturia

Endocrine and Metabolic Disorders

• Gynaecomastia

Musculoskeletal Disorders

• Myalgia
• Limb pain

Skin and Subcutaneous Tissue Disorders

• Steven-Johnson syndrome 
• Toxic epidermal necrolysis 
• Skin rash
• Cellulitis
• Alopecia

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Fluid retention
• Leukopenia

Sensory Disorders

• Retinal haemorrhage
• Visual impairment
• Blurred vision 
• Photophobia
• Reduced visual acuity 
• Diplopia
• Abnormal sensation in eye
• Non-arteritic anterior ischaemic optic neuropathy 
• Retinal vascular occlusion
• Visual field defect
• Vertigo
• Tinnitus
• Deafness

• Potent cytochrome P450 3A4 inhibitors
• Ritonavir
• Erythromycin
• Saquinavir
• Ketoconazole
• Itraconazole
• CYP450 inducers
• CYP450 inhibitors
• Phosphodiesterase-5-inhibitors
• Antihypertensive agents
• Nitric oxide donors
• Nitrates
• Organic nitrates
• Amyl nitrite
• Guanylate cyclase stimulators
• Vitamin K antagonists
• Alpha blockers
• Riociguat

Other interactions

• Grapefruit juice

None routine. Specific cases may require

• Vital signs
• Signs of pulmonary oedema

Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) enzyme. This enzyme is responsible for the degradation of cGMP. It is present in the corpus cavernosum of the penis as well as in smooth muscle cells of the pulmonary vasculature. Increase in cGMP results in relaxation of the pulmonary vascular bed. To a lesser degree, sildenafil also causes vasodilation in the systemic circulation.

Tablet 20mg

• Revatio (Pfizer) originator

Tablet 25mg

• Sildavee fct (Pharmacare)
• Viagra (UpJohn) originator

Tablet 50mg

• Avigra fct (Pharmacia)
• Dynafil (Pharma Dynamics)
• Lifaned 50 fct (Unichem)
• Raviag (Ranbaxy)
• Sildavee fct (Pharmacare)
• Sildenafil cipla (Cipla)
• Sildojub (LeBasi)
• Silwin (Winthrop) (Discontinued: 11/07/2018)
• Viagra fct (UpJohn) originator
• Videna (Adcock)
• Vitrixia 50 (Abex)

Tablet 100mg

• Actigra (Actavis)
• Actigra fct (Actavis)
• Avigra fct (Pharmacia)
• Dynafil (Pharma Dynamics)
• Lifaned 100 fct (Unichem)
• Raviag (Ranbaxy)
• Sildavee fct (Pharmacare)
• Sildojub (LeBasi)
• Silwin (Winthrop) (Discontinued: 11/07/2018)
• Sildenafil 100 Cipla fct (Cipla Medpro)
• Viagra (Pfizer) originator
• Videna (Adcock)
• Vitrixia 100 (Abex)

Tablet chew 50mg

• Zeldina (Camox)

Tablet chew 100mg

• Zeldina (Camox)