What are the considerations for a patient taking Tadalafil (generic name: Tadalafil) and prescribed Nitroglycerin (generic name: Nitroglycerin) for angina pectoris (chest pain)?

From the Guidelines

Tadalafil and nitroglycerin must never be taken together due to the risk of severe, potentially life-threatening hypotension. Patients should be instructed to avoid taking nitroglycerin in any form (sublingual tablets, spray, patches, or ointments) within at least 48 hours after taking tadalafil, as recommended by the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline 1. This dangerous interaction occurs because both medications work by increasing nitric oxide levels, which causes blood vessel dilation. When combined, they can cause an excessive drop in blood pressure that may lead to fainting, stroke, heart attack, or even death.

Key Considerations

• The patient should be advised to inform all healthcare providers about their tadalafil use and to wear a medical alert bracelet or carry information indicating they take tadalafil.
• Alternative treatments for chest pain should be discussed, and the patient should be instructed to seek immediate emergency care if chest pain occurs, making sure to inform emergency personnel about their tadalafil use.
• The consultation should also include clear documentation of this discussion in the patient's medical record, as emphasized in the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1.

Rationale

The rationale for avoiding concomitant use of tadalafil and nitroglycerin is based on the potential for severe hypotension, as highlighted in the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline 1 and the 2004 ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction 1. The patient's safety and well-being should be the top priority, and alternative treatments for chest pain should be explored to minimize the risk of adverse interactions.

Clinical Implications

In clinical practice, it is essential to prioritize the patient's safety and well-being by avoiding concomitant use of tadalafil and nitroglycerin. Healthcare providers should be aware of the potential risks and take necessary precautions to prevent adverse interactions, as recommended by the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1. By doing so, we can minimize the risk of severe hypotension and ensure the best possible outcomes for patients with angina pectoris.

From the FDA Drug Label

Physicians should discuss with patients the contraindication of tadalafil with regular and/or intermittent use of organic nitrates. Patients should be counseled that concomitant use of tadalafil with nitrates could cause blood pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke Physicians should discuss with patients the appropriate action in the event that they experience anginal chest pain requiring nitroglycerin following intake of tadalafil In such a patient, who has taken tadalafil, where nitrate administration is deemed medically necessary for a life-threatening situation, at least 48 hours should have elapsed after the last dose of tadalafil before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring

The patient taking Tadalafil and prescribed Nitroglycerin for angina pectoris should be aware of the following considerations:

• Concomitant use of Tadalafil and nitrates is contraindicated due to the risk of blood pressure dropping to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke.
• If anginal chest pain occurs after taking Tadalafil, the patient should seek immediate medical attention.
• If nitrate administration is medically necessary, at least 48 hours should have elapsed after the last dose of Tadalafil before nitrate administration is considered.
• Nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring 2.

From the Research

Considerations for Patients Taking Tadalafil and Prescribed Nitroglycerin

• The combination of Tadalafil and Nitroglycerin can lead to a synergistic decrease in blood pressure, resulting in hypotension 3.
• The interaction between Tadalafil and Nitroglycerin can last for up to 48 hours after Tadalafil administration, due to its longer elimination half-life 3.
• Patients taking Tadalafil should not receive Nitroglycerin, as this combination is contraindicated 3.
• Nitroglycerin is effective in treating angina pectoris, but its use can lead to side effects such as headache and postural hypotensive symptoms 4.
• The risk of adverse events, including hypotension, associated with Nitroglycerin administration can be increased in patients with certain characteristics, such as increasing age and heart rate 5, 6.

Factors Affecting the Risk of Adverse Events

• Increasing age is associated with an increased risk of adverse events, including hypotension, after Nitroglycerin administration 5, 6.
• Heart rate can also affect the risk of adverse events, with tachycardic patients showing an increased risk of hypotension 6.
• The presence of intravenous access prior to Nitroglycerin administration may reduce the risk of adverse events 5.
• Pre-existing blood pressure can also impact the risk of hypotension, with patients having a lower pre-Nitroglycerin blood pressure being more susceptible to hypotension 6.

Safety of Nitroglycerin Administration

• High-dose sublingual Nitroglycerin administration is rarely associated with hypotension, with an incidence of 3.2% in one study 7.
• The safety of Nitroglycerin administration can be improved by careful patient selection and monitoring, as well as the use of appropriate dosing regimens 4, 7.