Medical Uses of Sildenafil (Viagra)
Sildenafil is primarily FDA-approved for two major medical conditions: erectile dysfunction and pulmonary arterial hypertension, with established efficacy for improving exercise capacity and delaying clinical worsening in PAH patients. 1
Pulmonary Arterial Hypertension (PAH)
Sildenafil is a potent and highly specific phosphodiesterase type 5 (PDE-5) inhibitor that works by:
- Increasing cGMP levels in vascular smooth muscle
- Causing vasodilation in the pulmonary circulation
- Reducing mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR)
- Improving cardiac index 2
Efficacy in PAH
In the Sildenafil Use in Pulmonary Arterial Hypertension-1 (SUPER-1) study, sildenafil demonstrated significant improvements in:
- 6-minute walk distance (45-50m improvement over placebo)
- Pulmonary arterial pressure
- Functional class 3
FDA-approved dosing for PAH is 20mg three times daily, though clinical trials showed benefits at higher doses (40mg and 80mg TID) 3
Role in PAH Treatment Algorithm
Sildenafil is recommended as a first-line therapy for PAH patients, particularly those with:
- WHO Group I PAH
- NYHA Functional Class II-III symptoms
- Idiopathic etiology or PAH associated with connective tissue disease 1
It can be used as monotherapy or in combination with other PAH medications, particularly prostanoids 3
Special Considerations in PAH
- Sildenafil may prevent rebound pulmonary vasoconstriction after withdrawal of inhaled nitric oxide 3
- When combined with inhaled prostanoids like iloprost, sildenafil can achieve greater and more prolonged decreases in mPAP and PVR than either agent alone 3
- Sildenafil has also shown benefit in chronic thromboembolic pulmonary hypertension (CTEPH) 3
Erectile Dysfunction
Sildenafil was the first oral PDE5 inhibitor approved for erectile dysfunction treatment.
Mechanism and Efficacy
- Inhibits PDE-5 in corpus cavernosum, allowing smooth muscle relaxation and potentiating erections during sexual stimulation 4
- Effective for erectile dysfunction of various causes:
- Organic (e.g., diabetes, spinal cord injury)
- Psychogenic
- Mixed etiology 4
Dosing for Erectile Dysfunction
- Starting dose: 50mg taken as needed approximately 1 hour before sexual activity
- Dose range: 25-100mg based on efficacy and tolerability
- Maximum frequency: once daily 4
- Lower doses (25mg) recommended for:
- Elderly patients
- Hepatic or renal impairment
- Patients taking CYP3A4 inhibitors 4
Clinical Guidance
- The American Urological Association strongly recommends PDE5 inhibitors like sildenafil as first-line therapy for erectile dysfunction 3
- Instructions should be provided to maximize efficacy:
Safety Considerations
Cardiovascular Effects
- Sildenafil causes mild, transient reductions in blood pressure (approximately 8/5.5 mmHg) 6
- Absolute contraindication: Concomitant use with nitrates due to risk of severe hypotension 1, 6
- Generally safe in patients with stable cardiovascular disease who are not taking nitrates 6
Common Side Effects
- Headache (16%)
- Flushing (10%)
- Dyspepsia
- Nasal congestion
- Visual disturbances
- Dizziness (2%) 7
Special Populations
- Use with caution in:
- Severe renal or hepatic impairment
- Patients with spinal cord injury
- Elderly patients 1
- Dose adjustments needed when used with CYP3A4 inhibitors (ritonavir, ketoconazole, erythromycin) 4
Drug Interactions
- Safe to use with most antihypertensive medications (beta-blockers, alpha-blockers, diuretics, ACE inhibitors, calcium channel blockers) with only additive, not potentiating, blood pressure effects 8
- Monitor blood pressure when initiating therapy, especially during dose titration 2
By understanding these medical uses and considerations, healthcare providers can appropriately prescribe sildenafil for both pulmonary arterial hypertension and erectile dysfunction while minimizing risks and optimizing benefits for patients.