Drug Interaction Between Ambien (Zolpidem) and Tessalon Perles (Benzonatate)
There is no clinically significant drug interaction between Ambien (zolpidem) and Tessalon Perles (benzonatate), and these medications can be safely used together.
Mechanism and Metabolism
Zolpidem and benzonatate have distinct pharmacological profiles that do not overlap in ways that would create meaningful interactions:
Zolpidem is metabolized primarily through multiple cytochrome P450 pathways (including CYP3A4, CYP1A2, and CYP2C9), acts selectively on GABA-A receptors (particularly the omega-1 subtype), and functions as a sedative-hypnotic 1, 2.
Benzonatate (the active ingredient in Tessalon Perles) is a non-narcotic antitussive that works by anesthetizing stretch receptors in the respiratory passages and lungs, with no significant CNS depressant effects or CYP450 interactions.
Absence of Documented Interactions
The comprehensive evidence on zolpidem drug interactions demonstrates that clinically important interactions occur primarily with:
- CYP450 inducers (like rifampicin) that significantly reduce zolpidem efficacy 2
- CYP450 inhibitors (like ketoconazole, erythromycin, cimetidine) that enhance sedative effects 2
- CNS depressants (alcohol, benzodiazepines, opioids) that cause additive sedation 2, 3
Benzonatate does not fall into any of these categories 2.
Clinical Considerations
While the combination is safe, be aware of the following:
Monitor for excessive sedation if the patient is taking other CNS depressants concurrently, though this would not be attributable to the zolpidem-benzonatate combination specifically 3.
Standard zolpidem precautions apply: Use 5 mg in elderly patients, avoid next-morning activities requiring alertness within 7-8 hours of dosing, and be aware of potential cognitive impairment 4.
Benzonatate capsules must be swallowed whole to avoid local anesthetic effects in the mouth and throat, but this is unrelated to zolpidem coadministration.