Can a patient with an allergy to lisinopril (an angiotensin-converting enzyme (ACE) inhibitor) use Tessalon Perles (benzonatate), a cough suppressant?

Can a Patient with Lisinopril Allergy Use Tessalon Perles?

Yes, a patient with a lisinopril allergy can safely use Tessalon Perles (benzonatate), as there is no cross-reactivity between ACE inhibitors like lisinopril and benzonatate—these medications have completely different chemical structures, mechanisms of action, and allergen profiles. 1

Understanding the Medications

Lisinopril (ACE Inhibitor)

• Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor used primarily for hypertension and heart failure 2
• True allergic reactions to lisinopril include angioedema (occurring in <1% of patients, more frequently in blacks and women) and rash 3
• ACE inhibitor-induced cough (occurring in up to 20% of patients) is not an allergic reaction—it is a pharmacologic side effect caused by bradykinin and substance P accumulation 3

Benzonatate (Tessalon Perles)

• Benzonatate is a peripherally acting antitussive (cough suppressant) that works by anesthetizing vagal sensory nerve fibers and inhibiting voltage-gated sodium channels, particularly Nav1.7 1, 4
• It is chemically unrelated to ACE inhibitors—benzonatate is a polyethoxy ester of 4-(butylamino) benzoic acid 4
• FDA-approved for symptomatic relief of cough since 1958 1

Critical Distinction: Allergy vs. Side Effect

If the "Allergy" is Actually Cough

• ACE inhibitor-induced cough is NOT an allergic reaction and does NOT contraindicate benzonatate use 3
• The cough is a class effect occurring in 5-35% of ACE inhibitor users due to kininase inhibition, not immune-mediated hypersensitivity 3, 5
• Benzonatate can actually be used to treat ACE inhibitor-induced cough in patients who must continue ACE inhibitor therapy 3, 6
• In fact, benzonatate effectively controlled cough in 80% of patients in case series, including those with cough unresponsive to opioids 3

If the "Allergy" is True Angioedema

• Angioedema from lisinopril is a true allergic/hypersensitivity reaction occurring in <1% of patients 3
• This reaction is specific to ACE inhibitors (and potentially ARBs with caution) due to bradykinin accumulation 3
• Benzonatate has no effect on the renin-angiotensin-aldosterone system or bradykinin metabolism 4
• There is no mechanistic basis for cross-reactivity between ACE inhibitor-induced angioedema and benzonatate 1, 4

Safety Profile of Benzonatate

Known Adverse Reactions

• Hypersensitivity reactions to benzonatate itself can occur but are unrelated to ACE inhibitor allergies 1
• Potential adverse effects include: bronchospasm, laryngospasm (if capsule is chewed or sucked), sedation, dizziness, GI upset, and pruritus 1
• Critical safety warning: Deliberate or accidental overdose has resulted in death, particularly in children—capsules must be swallowed whole 1

No Cross-Reactivity Evidence

• The medical literature contains no reports of cross-reactivity between ACE inhibitors and benzonatate 1, 6
• These medications have entirely different chemical structures, pharmacologic targets, and metabolic pathways 2, 4

Clinical Recommendation Algorithm

Step 1: Clarify the Nature of the "Lisinopril Allergy"

• If the reaction was cough: This is not an allergy—benzonatate is safe and may even be therapeutic 3
• If the reaction was angioedema: This is a true hypersensitivity—benzonatate is still safe as there is no cross-reactivity 3, 1, 4
• If the reaction was rash or other hypersensitivity: Benzonatate is safe as it is chemically unrelated 1

Step 2: Prescribe Benzonatate with Standard Precautions

• Use standard dosing for symptomatic cough relief 1
• Counsel patient to swallow capsules whole (never chew or suck) to avoid local anesthetic effects and serious adverse reactions 1
• Monitor for benzonatate-specific adverse effects (sedation, dizziness, GI upset) unrelated to ACE inhibitor history 1

Common Pitfalls to Avoid

• Do not confuse ACE inhibitor-induced cough with a true allergy—cough is a pharmacologic side effect, not an immune-mediated reaction 3
• Do not assume all drug "allergies" represent true hypersensitivity—many reported allergies are actually predictable side effects 3
• Do not avoid benzonatate in patients with ACE inhibitor angioedema—there is no mechanistic basis for cross-reactivity between these structurally and pharmacologically distinct medications 1, 4
• Always instruct patients to swallow benzonatate capsules whole—chewing or sucking can cause serious local anesthetic effects including bronchospasm and laryngospasm 1