Sildenafil

Intravenous
Pulmonary arterial hypertension

Oral
Erectile dysfunction

Oral
Pulmonary arterial hypertension

Erectile dysfunction:
Patients receiving CYP3A4 inhibitors (e.g. erythromycin, ketoconazole, itraconazole, cimetidine): Initially, 25 mg.

Patients receiving ritonavir: Max dose: 25 mg for 48 hours.

Patients who are stable on α-blocker therapy: Initially, 25 mg.

Pulmonary arterial hypertension:
Oral
Patients receiving CYP3A4 inhibitors (e.g. erythromycin, saquinavir): 20 mg bid.

Patients receiving more potent CYP3A4 inhibitors (e.g. clarithromycin, telithromycin, nefazodone): 20 mg once daily.

Intravenous
Patients receiving CYP3A4 inhibitors (e.g. erythromycin, saquinavir): 10 mg bid.

Patients receiving more potent CYP3A4 inhibitors (e.g. clarithromycin, telithromycin, nefazodone): 10 mg once daily.

Oral:
Erectile dysfunction:

CrCl (mL/min)	Dosage
<30	Initially, 25 mg. May increase stepwise to 50 mg up to 100 mg as necessary based on efficacy and tolerability.

Intravenous:
Pulmonary arterial hypertension:
May decrease dose to 10 mg bid based on tolerability.

Oral:
Erectile dysfunction:
Mild to moderate: Initially, 25 mg. May increase stepwise to 50 mg up to 100 mg as necessary based on efficacy and tolerability. Severe: Contraindicated.

Intravenous:
Pulmonary arterial hypertension:
Mild to moderate (Child-Pugh class A and B): May decrease dose to 10 mg bid based on tolerability. Severe (Child-Pugh Class C): Contraindicated.

Sildenafil May be taken with or without food.

Powder for oral susp: Reconstitute with a total volume of 90 mL of water (added in 2 portions, 60 mL for the 1st addition followed by 30 mL for the 2nd addition) to provide a susp containing 10 mg/mL. Shake vigorously for at least 30 seconds after each addition.

Recent history of MI or stroke, severe hypotension (<90/50 mmHg); hereditary degenerative retinal disorders (e.g. retinitis pigmentosa); vision loss in 1 eye due to non-arteritic anterior ischaemic optic neuropathy (NAION); pulmonary hypertension secondary to sickle cell anaemia. When used for erectile dysfunction: Men for whom sexual activity is inadvisable (e.g. unstable angina, severe cardiac failure). Severe hepatic impairment. Concomitant use with nicorandil, nitric oxide donors, organic nitrates or nitrates in any form; guanylate cyclase stimulators (e.g. riociguat); potent CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir) when used for pulmonary arterial hypertension.

Patient with anatomical penis deformation (e.g. angulation, cavernosal fibrosis, Peyronie disease), predisposition to priapism (e.g. sickle cell anaemia, multiple myeloma, leukaemia); uncontrolled hypertension (>170/110 mmHg), life-threatening arrythmias, left ventricular outflow obstruction (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy), autonomic dysfunction; bleeding disorders; active peptic ulcer disease; pulmonary veno-occlusive disease. Patients taking CYP3A4 inhibitors, α-blockers and other PDE5 inhibitors. Renal and mild to moderate hepatic impairment. Elderly. Pregnancy and lactation (when used for pulmonary arterial hypertension).

Significant: Sudden auditory impairment and hearing loss; hypotension, hypertension; impaired color discrimination, visual disturbances (e.g. reversible cyanopsia, photophobia, blurred vision), anterior uveitis, macular oedema, retinal artery occlusion. Rarely, priapism, sudden vision loss or NAION.
Cardiac disorders: Tachycardia, palpitations, chest pain.
Ear and labyrinth disorders: Vertigo.
Gastrointestinal disorders: Nausea, vomiting, dyspepsia, GERD, upper abdominal pain, dry mouth.
General disorders and administration site conditions: Fatigue, pyrexia.
Immune system disorders: Hypersensitivity.
Investigations: Heart rate increased.
Musculoskeletal and connective tissue disorders: Myalgia, pain in extremity, back pain.
Nervous system disorders: Headache, dizziness, somnolence, hypoaesthesia, insomnia.
Psychiatric disorders: Anxiety.
Renal and urinary disorders: Haematuria.
Respiratory, thoracic and mediastinal disorders: Rhinitis, nasal or sinus congestion, epistaxis.
Skin and subcutaneous tissue disorders: Rash.
Vascular disorders: Flushing, hot flush.
Potentially Fatal: Serious CV events (e.g. MI, TIA, unstable angina, sudden cardiac death, ventricular arrythmia, cerebrovascular haemorrhage).

IV/PO: B

This drug may cause dizziness and visual disturbances, if affected, do not drive or operate machinery.

Physical examination and medical history must be undertaken to diagnose erectile dysfunction and identify possible underlying causes and appropriate treatment options. Assess CV status prior to treatment (when used for erectile dysfunction). Monitor blood pressure, pulse rate (particularly when used concomitantly with blood pressure lowering agents). Assess for signs and symptoms of pulmonary oedema.

Symptoms: Headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision. Management: Supportive and symptomatic treatment. Monitor blood pressure and ECG.

May enhance hypotensive effect with α-blockers and other antihypertensive drugs. May enhance the adverse/toxic effects with other PDE5 inhibitors. Increased serum concentration with ritonavir and CYP3A4 inhibitors (e.g. cimetidine, erythromycin, itraconazole, ketoconazole). May decrease serum concentration with CYP3A4 inducers (e.g. rifampicin) and bosentan.
Potentially Fatal: Enhanced hypotensive effect of nicorandil, nitric oxide donors (e,g. amyl nitrite), organic nitrates (e.g. nitroglycerin, sodium nitroprusside, isosorbide dinitrate) or nitrates in any form, and guanylate cyclase stimulators (e.g. riociguat).

May increase the risk of orthostatic hypotension with alcohol. May increase serum concentration with grapefruit juice (oral).

Description:
Mechanism of Action: Sildenafil is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible in the metabolism of cyclic guanosine monophosphate (cGMP). Nitric oxide is released during sexual stimulation and sildenafil enhances its effect by inhibiting PDE5, thus causing increased cGMP levels. This produces smooth muscle relaxation and inflow of blood into the penile tissue, thereby causing an erection. For pulmonary arterial hypertension, PDE5 inhibition results in pulmonary vascular smooth muscle relaxation. Additionally, vasodilation in the pulmonary bed and systemic circulation may also occur.
Onset: Erectile dysfunction: Approx 60 minutes.
Duration: Erectile dysfunction: 2-4 hours. Decrease blood pressure: <8 hours.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Decreased rate of absorption with food. Delayed absorption with high-fat meal. Bioavailability: 25-63%. Time to peak plasma concentration: 30-120 minutes.
Distribution: Widely distributed in the tissues. Crosses the placenta and enters breast milk. Plasma protein binding: Approx 96% (sildenafil and N-desmethyl metabolite).
Metabolism: Metabolised in the liver by CYP3A4 (major route) and CYP2C9 (minor route) via N-demethylation into N-desmethylsildenafil (major metabolite).
Excretion: Mainly via faeces (approx 80%, as metabolites); urine (approx 13%). Terminal elimination half-life: Approx 4 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135398744, Sildenafil. https://pubchem.ncbi.nlm.nih.gov/compound/Sildenafil. Accessed Nov. 26, 2024.

Store between 15-30°C. Oral suspension: Store below 30°C. Do not freeze. Storage recommendations may vary among individual products (refer to specific product guidelines).

Drugs for Erectile Dysfunction & Ejaculatory Disorders / Other Cardiovascular Drugs

G04BE03 - sildenafil ; Belongs to the class of drugs used in erectile dysfunction.

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