Sildenafil (Viagra)

Generic Name: Sildenafil
Brand Names: Viagra, Revatio (for pulmonary arterial hypertension)
Drug Class: Phosphodiesterase type 5 (PDE5) inhibitor
Formulations: Film-coated tablets, oral suspension, intravenous injection (Revatio only)
Route of Administration: Oral (Viagra), Oral/IV (Revatio)

Indications and Clinical Use

1. Erectile Dysfunction (ED)

   • Primary indication for Viagra brand.

   • Used to treat difficulty achieving or maintaining an erection sufficient for sexual activity.

   • Works only with sexual stimulation.

2. Pulmonary Arterial Hypertension (PAH)

   • Marketed under Revatio for treatment of WHO Group I PAH to improve exercise capacity and delay clinical worsening.

   • Used in adults and pediatric patients aged ≥1 year.

3. Off-Label Uses

   • Raynaud’s phenomenon

   • Female sexual arousal disorder

   • High-altitude pulmonary edema (HAPE) prevention

   • Potential fertility enhancement in select populations

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Mechanism of Action

Sildenafil selectively inhibits phosphodiesterase type 5 (PDE5), an enzyme found in high concentrations in the corpus cavernosum of the penis and pulmonary vasculature.

• Sexual stimulation leads to nitric oxide (NO) release in the corpus cavernosum

• NO activates guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP)

• cGMP causes smooth muscle relaxation and vasodilation, resulting in inflow of blood to the penis

• PDE5 normally degrades cGMP; inhibition enhances and prolongs erection

In pulmonary circulation, the same mechanism promotes vasodilation, reducing pulmonary vascular resistance and pressure.

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Dosage and Administration

For Erectile Dysfunction (Viagra)

• Initial Dose: 50 mg taken 1 hour before sexual activity

• Range: 25 mg to 100 mg once daily as needed

• Timing: Take on an empty stomach; fatty meals delay onset

• Maximum Frequency: Once per day

For Pulmonary Arterial Hypertension (Revatio)

• Oral: 20 mg three times daily (taken 4–6 hours apart)

• IV: 10 mg IV three times daily when oral administration is not feasible

• Pediatrics: Based on weight; dosing adjusted accordingly

Administration Advice

• Avoid grapefruit or grapefruit juice

• Do not combine with other PDE5 inhibitors or nitrates

• Dose adjustment may be necessary in hepatic or renal impairment

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Pharmacokinetics

• Bioavailability: ~40%

• Time to Peak: 30–120 minutes (median ~60 minutes)

• Protein Binding: ~96%

• Metabolism: Hepatic via CYP3A4 (major), CYP2C9 (minor)

• Half-life: 3–5 hours

• Excretion: Feces (80%), urine (13%)

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Contraindications

• Use of nitrates (e.g., nitroglycerin) due to risk of severe hypotension

• Concomitant use with riociguat (a guanylate cyclase stimulator)

• Severe hypotension (SBP <90 mmHg)

• Recent stroke, myocardial infarction, or unstable angina

• Retinitis pigmentosa (rare inherited retinal disorders)

• Severe hepatic impairment

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Warnings and Precautions

• Cardiovascular Risk: Use caution in patients with cardiovascular disease; assess fitness for sexual activity

• Hypotension: Risk of serious hypotension with nitrates, alpha-blockers, or antihypertensives

• Priapism: Erection lasting >4 hours may cause permanent damage; immediate medical attention required

• Vision Loss: Rare risk of non-arteritic anterior ischemic optic neuropathy (NAION)

• Hearing Loss: Sudden decrease or loss of hearing reported

• Hepatic/Renal Impairment: Dose reduction may be required

• Bleeding Risk: PDE5 inhibition may potentiate platelet aggregation inhibition; use cautiously with bleeding disorders

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Adverse Effects

Common (>2%)

• Headache

• Flushing

• Dyspepsia

• Nasal congestion

• Visual disturbances (blurred vision, blue tint)

• Back pain

• Myalgia

• Dizziness

Less Common/Serious

• Hypotension

• Priapism

• Sudden hearing or vision loss

• Cardiovascular events (angina, myocardial infarction, arrhythmia)

• Rash or hypersensitivity reactions

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Drug Interactions

1. CYP3A4 Inhibitors

   • Potent inhibitors (e.g., ketoconazole, ritonavir, clarithromycin) increase sildenafil levels

   • Reduce sildenafil dose (start at 25 mg for ED)

2. Nitrates (contraindicated)

   • Profound hypotension may occur; avoid co-administration completely

3. Alpha-blockers (e.g., tamsulosin)

   • Can enhance hypotensive effect; stable on alpha-blocker therapy before starting sildenafil

4. Antihypertensives

   • Additive BP-lowering effect possible

5. Riociguat (contraindicated)

   • Both increase cGMP; severe hypotension risk

6. Other PDE5 inhibitors (e.g., tadalafil, vardenafil)

   • Avoid concurrent use

7. Erythromycin, saquinavir

   • Moderate CYP3A4 inhibition; dose adjustment needed

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Monitoring Parameters

• Blood pressure (especially if using antihypertensives or alpha-blockers)

• Cardiovascular tolerance to sexual activity

• Signs of vision or hearing changes

• Priapism symptoms

• Efficacy in terms of improved erectile function or exercise capacity (Revatio)

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Use in Special Populations

• Pregnancy: Category B for PAH (Revatio); not indicated in women for ED

• Lactation: Avoid—no data available

• Pediatrics: Approved for PAH in children ≥1 year under Revatio

• Geriatrics: Increased sensitivity possible; start at lower doses

• Renal/Hepatic Impairment: Reduce starting dose to 25 mg

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Comparative Aspects (PDE5 Inhibitors)

Drug	Onset	Duration	Fatty Food Effect	Dosing Frequency
Sildenafil	30–60 min	~4 hrs	Delays onset	PRN (1/day)
Tadalafil	30–45 min	24–36 hrs	Minimal	Daily or PRN
Vardenafil	30–60 min	4–5 hrs	Delays onset	PRN (1/day)
Avanafil	15–30 min	6 hrs	Minimal	PRN (1/day)

Viagra vs. Revatio

• Viagra is dosed higher (25–100 mg) and taken as needed for ED

• Revatio is used continuously at lower doses (20 mg TID) for PAH

• Formulations differ slightly, but both contain sildenafil citrate

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Storage and Stability

• Store tablets at room temperature (20–25°C)

• Protect from moisture and direct sunlight

• Oral suspension (Revatio) should be shaken well and used within specified period once reconstituted

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Patient Counseling Points

• Take sildenafil approximately 1 hour before sexual activity

• Sexual stimulation is necessary for the drug to work

• Avoid heavy meals (especially fatty foods) before dosing

• Do not exceed one dose per 24 hours

• Report any sudden vision or hearing loss

• Stop and seek emergency help for chest pain during sex

• Seek immediate care for erections lasting more than 4 hours

• Do not use with nitrate medications

• Inform all providers (including dentists) of sildenafil use

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Regulatory Classification and Availability

• Prescription-only in most countries

• Available as brand (Viagra, Revatio) and generics

• Included in many national formularies

• Not a controlled substance

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Global Brand Examples

• Viagra (Pfizer, now generic globally)

• Revatio (Pfizer/Viatris)

• Suhagra, Penegra, Kamagra, Silagra – generic names in India

• Vizarsin, Eriacta, Sildalis – other generics globally