What are the contraindications for sildenafil (Revatio) 20mg in patients with pulmonary arterial hypertension (PAH)?

Contraindications for Sildenafil 20mg in Pulmonary Arterial Hypertension

Sildenafil 20mg is absolutely contraindicated in patients taking nitrates in any form and in those taking riociguat due to potentially life-threatening hypotension. 1, 2

Primary Contraindications

• Concomitant nitrate use: Sildenafil is strictly contraindicated with any nitrate medications (including nitroglycerin in any form, isosorbide mononitrate/dinitrate, and recreational "poppers") due to potentially fatal hypotension 1

• Concomitant riociguat use: The combination of sildenafil with riociguat (a soluble guanylate cyclase stimulator) is contraindicated due to severe hypotension and other relevant side effects detected in clinical trials 2

• Hypersensitivity: Patients with known hypersensitivity to sildenafil or any component of the formulation 1

Drug Interactions Requiring Caution or Dose Adjustment

• CYP3A4 inhibitors: Medications that inhibit CYP3A4 can significantly increase sildenafil levels:

  • Ketoconazole, itraconazole: May increase sildenafil levels 2, 3
  • Fluconazole: Can considerably increase sildenafil levels, requiring dose reduction of approximately 60% 3
  • Ritonavir and other HIV protease inhibitors: Markedly increase sildenafil levels, requiring dose adjustment 2
  • Erythromycin: Increases sildenafil levels 2

• Other medications:

  • Bosentan: Reduces sildenafil levels by approximately 50% while sildenafil increases bosentan levels by 50% 2
  • Cyclosporine: Requires caution when co-administered 2
  • Cimetidine: May increase sildenafil levels 2

Relative Contraindications and Cautions

• Severe hepatic impairment: May require dose adjustment

• Severe renal impairment: May require dose adjustment

• Anatomical penile deformities or conditions predisposing to priapism 1

• Recent history of stroke or myocardial infarction: Caution is advised due to potential cardiovascular effects 4

• Retinitis pigmentosa: Caution is advised in patients with this rare hereditary eye condition 1

• History of non-arteritic anterior ischemic optic neuropathy (NAION): Patients with previous NAION may be at increased risk of recurrence 1

Monitoring Recommendations

• Blood pressure monitoring: Particularly important when initiating therapy and with dose adjustments

• Visual function: Patients should be advised to seek immediate medical attention for sudden vision changes 1

• Hearing: Patients should report sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness 1

Special Populations

• Pregnancy: Limited data available; use only if potential benefit justifies potential risk to the fetus 1

• Breastfeeding: Unknown if sildenafil passes into breast milk; use caution 1

Dosing Considerations

The approved dose for PAH is 20mg three times daily. Higher doses up to 80mg TID may be used in selected patients based on recent evidence showing non-inferiority in mortality and potential benefits in exercise capacity, though with potentially increased adverse events 5.

Common Pitfalls to Avoid

1. Failure to recognize nitrate contraindication: Always thoroughly review all medications, including as-needed and over-the-counter products, for nitrate content

2. Overlooking drug interactions: Particularly with antifungals, HIV medications, and other PAH therapies

3. Inadequate patient education: Patients must understand the importance of not taking other PDE-5 inhibitors (such as those prescribed for erectile dysfunction) concurrently with sildenafil for PAH 1

4. Missing symptoms of adverse effects: Monitor for headache, flushing, epistaxis, and dyspepsia, which are common side effects 2