Does Paxlovid (nirmatrelvir and ritonavir) interfere with thyroid medications, such as levothyroxine, in patients with a history of thyroid disease?

Does Paxlovid Interfere with Thyroid Medications?

Paxlovid (nirmatrelvir/ritonavir) does not have clinically significant direct interactions with levothyroxine or other thyroid hormone replacement medications, and thyroid medications can be safely continued during the 5-day Paxlovid treatment course without dose adjustment.

Understanding the Interaction Profile

The ritonavir component of Paxlovid is a potent CYP3A4 inhibitor that can cause significant drug-drug interactions with medications metabolized through this pathway 1. However, levothyroxine is not metabolized by CYP3A4 and therefore is not subject to this primary mechanism of interaction 1.

Thyroid Medication Absorption and Metabolism

Levothyroxine absorption occurs primarily in the small intestine and is not significantly affected by short-term medications like Paxlovid 2. The main pathways for drug interactions with thyroid hormones include:

• Inhibition of thyroid hormone synthesis or release 3
• Alterations in thyroid hormone transport proteins 4
• Changes in thyroid hormone metabolism through deiodination 2
• Direct interference with levothyroxine absorption through chelation or pH changes 2

Paxlovid does not operate through any of these mechanisms 1.

Clinical Management Recommendations

• Continue levothyroxine at the current dose throughout the 5-day Paxlovid course without interruption 1
• Maintain standard levothyroxine administration timing (on empty stomach, 30-60 minutes before breakfast) 5
• No additional thyroid function monitoring is required specifically due to Paxlovid use 1
• Separate Paxlovid dosing from levothyroxine by at least 30-60 minutes if taken in the morning, though this is a general precaution rather than a specific interaction concern 2

Important Caveats for Specific Situations

For patients with pre-existing thyroid disease requiring careful TSH control:

• The short 5-day course of Paxlovid is insufficient to cause meaningful changes in thyroid hormone levels, as levothyroxine has a half-life of approximately 7 days and requires 6-8 weeks to reach steady state after dose changes 5

For patients on multiple medications:

• Review other comedications for potential interactions with Paxlovid, as ritonavir can significantly affect drugs metabolized by CYP3A4, including some cardiac medications, anticoagulants, and immunosuppressants 1
• Thyroid medications themselves remain safe, but other drugs the patient takes may require temporary adjustment 1

For patients with thyroid cancer requiring TSH suppression:

• Continue levothyroxine without modification, as the brief Paxlovid course will not affect TSH suppression targets 5

Drugs That DO Interact with Levothyroxine (Not Paxlovid)

To provide context, medications that genuinely interfere with thyroid hormone include:

• Calcium and iron supplements - reduce absorption through chelation 2
• Proton pump inhibitors - decrease absorption through pH changes 2
• Bile acid sequestrants - bind levothyroxine in the gut 2
• Tyrosine kinase inhibitors - can cause primary hypothyroidism 3, 6
• Amiodarone and lithium - affect thyroid hormone synthesis 3, 6

Paxlovid is not among these interacting medications 1.

Monitoring Recommendations

• No change in routine thyroid monitoring schedule is needed due to Paxlovid 7
• If TSH monitoring was already planned, proceed as scheduled (typically every 6-8 weeks during dose titration or every 6-12 months for stable patients) 5
• Only recheck thyroid function if new symptoms of hypo- or hyperthyroidism develop, which would be unrelated to the brief Paxlovid course 5

Critical Safety Point

The primary concern with Paxlovid is its interaction with CYP3A4-metabolized drugs, not thyroid medications 1. Always review the complete medication list for other potential interactions, particularly with cardiovascular drugs, anticoagulants, immunosuppressants, and certain psychiatric medications 1.