Do naloxone, Versed (midazolam), fentanyl, or Romazicon (flumazenil) contain shellfish components in patients with a known shellfish allergy?

Naloxone, Versed, Fentanyl, and Romazicon Do Not Contain Shellfish Components

None of these medications—naloxone, Versed (midazolam), fentanyl, or Romazicon (flumazenil)—contain shellfish components, and patients with shellfish allergies can safely receive all of them without special precautions or premedication. 1

Understanding the Shellfish Allergy Misconception

The concern about shellfish allergies and medications stems from a persistent medical myth that has been thoroughly debunked:

• Shellfish allergies are caused by tropomyosin proteins (a muscle protein found in crustaceans and mollusks), not by iodine or any component used in pharmaceutical manufacturing 1, 2, 3, 4

• Iodine is not an allergen—it is an essential trace element required for human life and cannot trigger immune responses 1, 2

• The American College of Radiology and American Academy of Allergy, Asthma & Immunology explicitly state that patients with shellfish or seafood allergies are not at elevated risk for reactions to iodine-containing products compared to the general population 1, 2

Specific Medication Safety Profile

Naloxone (Opioid Antagonist)

• Naloxone is structurally related to oxymorphine and contains no shellfish-derived components 1
• It can be safely administered to patients with shellfish allergies without any contraindications related to seafood sensitivities 1
• The only relevant precautions involve patients with chronic opioid use (risk of precipitating withdrawal), not allergies 1

Versed/Midazolam (Benzodiazepine)

• Midazolam is a synthetic water-soluble benzodiazepine with no shellfish components 1
• Shellfish allergy is not a contraindication for midazolam administration 1
• Standard dosing and monitoring apply regardless of shellfish allergy status 1

Fentanyl (Synthetic Opioid)

• Fentanyl is a fully synthetic opioid narcotic that contains no shellfish-derived ingredients 1
• It can be safely administered to patients with shellfish allergies 1
• The primary adverse effects (respiratory depression, chest wall rigidity) are unrelated to allergic mechanisms 1

Romazicon/Flumazenil (Benzodiazepine Antagonist)

• Flumazenil is a competitive benzodiazepine receptor antagonist with no shellfish components 1
• Shellfish allergy is not a contraindication for flumazenil use 1
• The contraindications for flumazenil relate to seizure risk and benzodiazepine dependence, not food allergies 1

Clinical Decision-Making Algorithm

When evaluating medication safety in shellfish-allergic patients:

1. Confirm the actual allergen: Shellfish allergies involve IgE antibodies to tropomyosin and other muscle proteins, not pharmaceutical excipients 3, 5, 4, 6

2. Distinguish from iodine misconception: The myth that shellfish allergy equals iodine allergy arose from a flawed 1975 survey showing equal rates of milk and egg allergies in contrast-reactive patients 1

3. Proceed with standard administration: No premedication, dose adjustment, or special monitoring is required for naloxone, midazolam, fentanyl, or flumazenil in shellfish-allergic patients 1

Common Pitfalls to Avoid

• Do not withhold or delay these medications based solely on shellfish allergy history—this creates unnecessary risk without any evidence-based benefit 1

• Do not confuse shellfish allergy with contrast media reactions: Even for iodinated contrast agents (which these medications are not), shellfish allergy does not predict contrast reactions 1

• Do not order unnecessary premedication: Administering steroids or antihistamines based on shellfish allergy alone has "a small but non-zero risk of adverse effect without any demonstrated benefit" 1

• Focus on actual drug allergies: If a patient has a documented allergy to one of these specific medications (not shellfish), that requires appropriate management—but this is unrelated to seafood sensitivities 1, 7

Evidence Quality and Consensus

The evidence supporting safe administration comes from multiple high-quality guidelines:

• The 2011 ACCF/AHA/SCAI guidelines (Circulation) provide Level C evidence that shellfish allergy prophylaxis for medication reactions is not beneficial 1

• The 2024 European Kidney Function Consortium consensus explicitly states that "shellfish allergy or an allergic-like reaction to topical povidone-iodine is not a contraindication" for iodinated agents 1

• The 2023 American Heart Association guidelines on poisoning management make no mention of shellfish allergy as a consideration for naloxone or flumazenil administration 1

Bottom line: Administer these medications using standard protocols without modification for shellfish allergy. The shellfish allergy is irrelevant to the safety profile of naloxone, Versed, fentanyl, and Romazicon. 1, 2