What medications are contraindicated with tadalafil (Cialis)?

Medications Contraindicated with Tadalafil (Cialis)

Nitrates in any form are absolutely contraindicated with tadalafil due to the risk of potentially fatal hypotension. Patients must wait at least 48 hours after taking tadalafil before using any nitrate medication. 1, 2

Major Contraindicated Medications

1. Nitrates (Absolute Contraindication)

• Organic nitrates in ALL forms:
  • Sublingual nitroglycerin tablets/spray
  • Transdermal nitroglycerin patches
  • Intravenous nitroglycerin
  • Isosorbide dinitrate/mononitrate (oral, sublingual)
  • Pentaerythritol tetranitrate
  • Erythritol tetranitrate

The combination of tadalafil with nitrates can cause severe, potentially life-threatening hypotension due to synergistic vasodilatory effects 2, 1. This occurs because both medications affect the nitric oxide-cGMP pathway, with tadalafil inhibiting the breakdown of cGMP while nitrates increase its production.

2. Guanylate Cyclase (GC) Stimulators

• Riociguat and other GC stimulators are contraindicated with tadalafil 1
• These medications also affect the nitric oxide pathway and can cause dangerous hypotension when combined with PDE5 inhibitors

Medications Requiring Caution

1. Alpha-Blockers

• Doxazosin, tamsulosin, alfuzosin, terazosin
• Combination may cause significant blood pressure reduction 1, 3
• Recommendations:
  • Use lowest possible dose of tadalafil
  • Only combine when patient is hemodynamically stable on alpha-blocker therapy
  • Monitor blood pressure closely

2. Antihypertensive Medications

• While not contraindicated, tadalafil can enhance the blood-pressure-lowering effects of:
  • ACE inhibitors
  • Angiotensin II receptor blockers
  • Beta-blockers
  • Calcium channel blockers
  • Diuretics
• Generally produces small, clinically manageable additive effects on blood pressure 1, 3

3. Alcohol

• Substantial alcohol consumption (≥5 units) with tadalafil increases the risk of:
  • Orthostatic hypotension
  • Increased heart rate
  • Dizziness
  • Headache 1

4. CYP3A4 Inhibitors

• Tadalafil is primarily metabolized by CYP3A4
• Strong inhibitors can significantly increase tadalafil exposure:
  • Ketoconazole, itraconazole
  • Ritonavir, atazanavir and other HIV protease inhibitors
  • Clarithromycin, erythromycin
  • Grapefruit juice

Clinical Implications and Safety Considerations

1. Timing considerations with nitrates:

   • In a medical emergency requiring nitrates after tadalafil use, at least 48 hours should elapse since the last tadalafil dose
   • Even then, nitrates should only be administered under close medical supervision with hemodynamic monitoring 2, 1

2. Patient education:

   • Patients taking tadalafil should be instructed to seek immediate medical attention if experiencing chest pain
   • They should inform emergency healthcare providers about tadalafil use to avoid inadvertent nitrate administration

3. Cardiovascular risk assessment:

   • Before prescribing tadalafil, consider the patient's cardiovascular status
   • Patients with unstable angina, recent MI (within 2 weeks), or uncontrolled hypertension should not receive tadalafil 2

The combination of tadalafil with nitrates remains the most dangerous potential drug interaction, with multiple guidelines and the FDA label emphasizing this absolute contraindication. While other medications may require caution or dose adjustments, they generally don't represent absolute contraindications when used appropriately.