Can Ascomp (acetaminophen, codeine) and Nurtec (rimegepant) be prescribed together for an adult patient with a history of migraines or chronic pain?

Can Ascomp (Acetaminophen/Codeine) and Nurtec (Rimegepant) Be Prescribed Together?

Yes, Ascomp (acetaminophen with codeine) and Nurtec (rimegepant) can be prescribed together, as there are no known drug interactions between these medications and they work through different mechanisms—codeine is an opioid analgesic while rimegepant is a CGRP receptor antagonist. 1

Mechanism and Safety Profile

• Rimegepant (Nurtec) is a calcitonin gene-related peptide (CGRP) receptor antagonist with no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials, making it safe for combination use 1
• Acetaminophen/codeine combinations work through central opioid receptor activation and peripheral prostaglandin inhibition, representing a completely different mechanism from CGRP antagonism 2
• There are no documented pharmacokinetic or pharmacodynamic interactions between opioid/acetaminophen combinations and CGRP antagonists 1, 2

Critical Clinical Considerations

However, this combination should be used with extreme caution and only as a last resort, not as routine therapy. Here's why:

• Opioids like codeine should be reserved only for cases where other medications cannot be used, when sedation effects are not a concern, or when the risk for abuse has been addressed 3, 4
• The American Academy of Neurology advises against using opioids or codeine-containing compounds for migraine treatment due to questionable efficacy, risk of dependency, rebound headaches, and eventual loss of efficacy 5, 4
• Codeine has significant limitations as a prodrug requiring CYP2D6 metabolism to achieve analgesic effects, with genetic polymorphisms (more common in Asians) potentially reducing response 3

Medication-Overuse Headache Risk

• Limit all acute migraine medications, including both Ascomp and Nurtec, to no more than 2 days per week to prevent medication-overuse headache 3, 4
• Using acute medications more than twice weekly creates a vicious cycle of increasing headache frequency and can lead to daily headaches 5, 4
• If the patient requires acute treatment more than twice weekly, initiate preventive therapy immediately rather than increasing acute medication frequency 5, 4

Preferred Alternative Approach

A better strategy would be to use rimegepant alone or in combination with NSAIDs rather than with codeine:

• Rimegepant represents a first-line option for moderate to severe migraine and can be used for both acute treatment and prevention 1
• NSAIDs (ibuprofen 400-800mg, naproxen 500-825mg) combined with rimegepant would provide superior efficacy without the risks associated with opioid use 4
• Acetaminophen alone (1000mg) can be combined with rimegepant if NSAIDs are contraindicated, avoiding the opioid component entirely 3

When This Combination Might Be Justified

The combination of Ascomp and Nurtec might only be appropriate in these specific scenarios:

• Patient has documented failure of all non-opioid alternatives including NSAIDs, triptans, and gepants as monotherapy 3
• Cardiovascular contraindications prevent use of triptans 5
• Severe pain requiring multimodal analgesia where sedation is acceptable 3
• Risk of opioid abuse has been thoroughly assessed and addressed 3, 4
• Short-term use only (not exceeding 2 days per week total) 4

Common Pitfall to Avoid

Do not establish a pattern where patients routinely combine opioids with newer migraine-specific medications like rimegepant. This undermines the superior safety profile of CGRP antagonists and creates unnecessary risks of dependency and medication-overuse headache 5, 4. Instead, optimize the rimegepant dosing and timing (take early in attack while pain is mild) before adding any opioid 4.