Can Paxlovid (nirmatrelvir and ritonavir) increase blood pressure in patients, particularly those with pre-existing hypertension or cardiovascular disease?

Can Paxlovid Increase Blood Pressure?

Paxlovid (nirmatrelvir/ritonavir) does not directly increase blood pressure and is not associated with hypertension as an adverse effect. The primary cardiovascular concern with Paxlovid relates to drug-drug interactions with antihypertensive medications rather than direct blood pressure elevation.

Evidence for Cardiovascular Safety

• Recent research demonstrates that Paxlovid use is associated with lower risks of cardiovascular complications in COVID-19 patients, including reduced rates of arrhythmias, heart failure, and major adverse cardiac events 1
• The medication showed protective cardiovascular effects with significantly lower mortality rates (HR = 0.21) and ICU admission rates (HR = 0.52) compared to non-Paxlovid groups 1
• No direct hypertensive effects have been documented in clinical trials or post-marketing surveillance of nirmatrelvir/ritonavir 2, 3

Critical Drug Interaction Concerns

The real clinical issue is ritonavir's interaction with blood pressure medications, not blood pressure elevation itself. Ritonavir is a potent inhibitor of CYP3A4 and P-glycoprotein, which can alter the metabolism of many cardiovascular drugs 3, 4.

Specific Antihypertensive Interactions

• Calcium channel blockers (particularly amlodipine, nifedipine): Ritonavir significantly increases their plasma concentrations, potentially causing excessive hypotension rather than hypertension 2, 3
• Beta-blockers metabolized by CYP2D6 (metoprolol, carvedilol): May have increased concentrations leading to bradycardia and hypotension 3
• ACE inhibitors and ARBs: Generally safe with minimal interactions, as they are not primarily CYP3A4 substrates 4
• Diuretics: No significant interactions expected 4

Management Algorithm for Hypertensive Patients

Before Prescribing Paxlovid

• Review all current antihypertensive medications for potential drug-drug interactions, focusing on CYP3A4 substrates 2, 3
• Identify high-risk medications including calcium channel blockers and certain beta-blockers that may require dose adjustment or temporary discontinuation 3
• Assess baseline blood pressure control to establish a reference point 5

During Paxlovid Treatment (5-day course)

• Monitor blood pressure closely if patients are on interacting antihypertensives, watching for hypotension rather than hypertension 2
• Consider temporary dose reduction of calcium channel blockers by 50% or more during the 5-day treatment course 3
• Switch to non-interacting alternatives when feasible (e.g., ACE inhibitors, ARBs, or thiazide diuretics) 4
• Avoid abrupt discontinuation of beta-blockers due to rebound hypertension risk 6

Post-Treatment Monitoring

• Resume normal antihypertensive dosing 2-3 days after completing Paxlovid, as CYP3A4 activity recovers within 3-5 days 7
• Monitor for rebound hypertension if medications were held or reduced 6

Common Pitfalls to Avoid

• Do not assume Paxlovid causes hypertension - the evidence shows no direct hypertensive effect and actually demonstrates cardiovascular protective benefits 1
• Do not overlook hypotension risk from drug interactions with calcium channel blockers, which is the more likely adverse effect 2, 3
• Do not continue full doses of CYP3A4-metabolized antihypertensives without adjustment during Paxlovid treatment 3
• Do not forget to reinitiate or up-titrate antihypertensives after completing the 5-day Paxlovid course 7

Special Populations

Patients with Pre-existing Cardiovascular Disease

• These patients are priority candidates for Paxlovid due to higher risk of severe COVID-19 progression 3
• The cardiovascular benefits of treating COVID-19 with Paxlovid outweigh drug interaction risks when properly managed 1
• Older patients (≥65 years) show even greater cardiovascular benefit from Paxlovid treatment 1

Patients on Multiple Cardiovascular Medications

• Among the top 100 prescribed medications in the US, 70 drugs have no expected interactions with Paxlovid, including many cardiovascular agents 4
• 30 drugs require management, but most can be safely adjusted for the 5-day treatment period 4
• ACE inhibitors, ARBs, and thiazide diuretics are generally safe options during Paxlovid treatment 4