Benzonatate
peripherally acting antitussive; PABA-type local anesthetic, related to tetracaine
Also sold as Tessalon, Tessalon Perles.
Findings for this medication
Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.
Benzonatate has no known classical depletion machinery, and its evidence base for nutrients is close to empty. The label is silent on absorption, elimination, nutrients, minerals, methemoglobinemia and food interactions apart from a swallow-whole instruction [1]. Its one documented metabolic step is hydrolysis by plasma butyrylcholinesterase to 4-(butylamino)benzoic acid, with no CYP enzyme listed [4][5][6]. A 2023 systematic review of 37 benzonatate articles found that safety evidence is dominated by overdose toxicity, with a high risk of bias [12]. No source located measured a vitamin, mineral or trace element in a benzonatate user.
peripherally acting antitussive; PABA-type local anesthetic, related to tetracaine · ATC R05DB01 (WHO ATC/DDD Index [2]) · also sold as Tessalon and Tessalon Perles and Zonatuss; many generics · reviewed 2026-10-07. This describes research about the medication. It does not say anything about your own levels or health.
How to read the evidence grades
These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.
Grades describe how strongly a finding can be attributed to Benzonatate in the research — not how common it is, how serious it would be, and not anything about you personally.
- Red — Severe
- Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
- Orange — Moderate
- At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
- Yellow — Low
- Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
- Not graded — disclosed evidence gap
- Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.
What the research found
Dietary intake: transient oropharyngeal numbness and choking when the capsule is broken
Yellow — LowSee study details
Direction: reduced intake, short-lived and behavioral. If a capsule is chewed, dissolved or broken, mouth and throat numbness and choking can occur, and the label says to avoid eating or drinking until it clears. No nutrient was measured and no deficiency is implied.
Full detail and limits
Dietary intake: transient oropharyngeal numbness and choking when the capsule is broken
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow
Limits on what this shows
- Null findings: None for benzonatate. Context only, Tier C and not about this drug: in 5 healthy volunteers a bilateral superior laryngeal nerve block raised penetration and aspiration with liquid, while the authors noted that topical anesthesia in other studies caused little impairment [24].
- At-risk subgroups: Children (accidental or chewed ingestion), and anyone who chews or sucks capsules [1][3]. Patients with swallowing impairment are an inference and are not addressed by any source opened.
Regulatory status
Label precaution (Tier A, this drug): capsules are to be swallowed whole; release of drug in the mouth can cause temporary oral numbness and possible choking; with numbness or tingling of the tongue, mouth, throat or face, avoid eating and drinking until it resolves, and seek care if symptoms worsen or persist [1]. The FDA 2010 safety communication states the same, adding that capsules are not to be broken, chewed, dissolved or crushed [3]. The label also lists constipation, nausea and GI upset, and sedation and dizziness, as adverse reactions, without frequencies in the text retrieved [1].
Population evidence
None quantifying intake change. The 2023 systematic review of 37 articles found safety data mostly about overdose or inappropriate use, with high risk of bias [12]. No study of food or fluid intake, weight, or nutrient status in benzonatate users was located.
Mechanism
Present (class H, changed intake): local anesthesia of the oropharynx on contact with released drug [1]. Whether swallowing or aspiration risk rises at therapeutic dosing when capsules are swallowed intact is not established by any source opened.
Counter-evidence held on record
Counter-evidence and confounding The effect lasts only while numbness persists, which the label frames as a reason to wait before eating or drinking. Cough, the indication, can itself limit eating. No evidence shows nutritional consequences. Framing caution This is an administration-safety instruction, not a nutrient depletion claim (Hard Rule 2). Do not suggest supplements or dietary changes from this entry.
Electrolytes in overdose cardiotoxicity: drug toxicity context, neutral direction
Yellow — LowSee study details
Overdose causes sodium channel blockade with seizures, dysrhythmia and cardiac arrest. This is the drug's own toxicity, not a nutrient or electrolyte deficiency; the electrolytes reported in two case reports were not depleted.
Full detail and limits
Electrolytes in overdose cardiotoxicity: drug toxicity context, neutral direction
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow
Limits on what this shows
- Null findings: Sodium, potassium and chloride were normal in the one case with values [10]. No source reported low magnesium, calcium or phosphate.
- At-risk subgroups: Children under 10 (accidental), adolescents and young adults with intentional ingestion, and patients taking other CNS or cardioactive drugs [1][3][7][8][11].
Regulatory status
Label overdosage section (Tier A, this drug): signs within 15 to 20 minutes; CNS stimulation then convulsions, coma, cerebral edema and cardiac arrest reported within 1 hour of ingestion; treatment is supportive, with a direction not to use CNS stimulants [1]. FDA 2010: 31 overdose cases in the adverse event system through May 19, 2010, including 7 accidental pediatric ingestions, 5 of them fatal in children aged 2 or younger [3].
Population evidence
Winter 2010 [7]: retrospective poison-center review, 2,172 single-substance ingestions (2000 to 2006); 116 (5%) serious outcomes (81 moderate, 31 major) and 4 deaths; dysrhythmias occurred in all fatalities, seizures did not. Minhaj 2021 [8]: systematic review plus poison-center fatality module, 36 cases (28 self-harm); cardiac arrest in 29, seizures in 24, dysrhythmias in 24; return of circulation in 23 of 28 resuscitated, 5 with good neurologic outcome (abstract read via a reconstructed OpenAlex record). Billington 2020 [10]: one 14-year-old, about 14 capsules of 200 mg; torsades de pointes arrest; QRS 83 to 111 ms, peak QTc 553 ms; serum Na 139, K 3.9, Cl 107, bicarbonate 18; magnesium sulfate 1 g given but no serum magnesium reported; full neurologic recovery. Jin 2019 [9]: one 37-year-old, fewer than 30 capsules with alcohol; pH 6.87 with mixed acidosis; died; no electrolyte values reported; no methemoglobin measured.
Mechanism
Named: voltage-gated sodium channel blockade (SCN5A listed as target) [4][9][10]; an educational summary agrees [13]. The acidosis in the case reports followed arrest. None of this operates through a nutrient.
Counter-evidence held on record
Counter-evidence and confounding Case reports cannot show electrolyte effects of the drug: magnesium, bicarbonate and other treatments were given before or alongside the reported values. Serum drug levels were not obtained in either case [9][10]. Framing caution This entry exists to record drug toxicity so it is not mistaken for a nutrient finding. It is not a deficiency claim. Overdose is a poison-center emergency, and no supplement addresses it.
The five body-system areas
Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.
Mitochondrial Burden
Each finding below is counted once, in this area only.
Mitochondrial burden: class extrapolation from local anesthetics, benzonatate not tested
Yellow — LowSee study details
Local anesthetics as a class reach mitochondria and lower membrane potential in living cells, and tetracaine, the closest named relative, inhibits mitochondrial ATPase in vitro. No study tested benzonatate.
Full detail and limits
Mitochondrial burden: class extrapolation from local anesthetics, benzonatate not tested
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow
Limits on what this shows
- Null findings: None located for benzonatate. No benzonatate cytotoxicity or mitochondrial assay was found in one benzonatate-specific web query (the class queries returned only local anesthetic records).
Regulatory status
Not mentioned in the benzonatate label [1].
Population evidence
None in humans for any local anesthetic at therapeutic oral exposure. Grouselle 1990 [19] (abstract only): in cultured cells, local anesthetics entered mitochondria and reversibly lowered or abolished transmembrane potential (rhodamine 123 dye), with size of effect tracking lipid solubility; the individual agents tested were not captured on the page. Adade 1984 [18] (abstract only): tetracaine, lidocaine, dibucaine and chlorpromazine partially, noncompetitively inhibited an isolated mitochondrial ATPase preparation. A 2010 hypothesis review states local anesthetics affect oxidative phosphorylation in isolated mitochondria in a structure-dependent way (electron transport, F1 ATPase, uncoupling), and that cardiolipin as a target lacks experimental evidence [20].
Mechanism
Plausible but unproven for benzonatate: membrane partitioning and enzyme inhibition by lipophilic local anesthetics in vitro. Whether benzonatate reaches mitochondria after oral dosing, at what concentration, or shares tetracaine's behavior was not assessed in any source opened.
Class cohort test
CLASS EXTRAPOLATION. Benzonatate was not in any cohort or preparation: it is absent from [18], [19] (agents not named) and [20]. Tetracaine, the structurally related ester anesthetic, was in [18]. Capped at yellow (Tier C).
Counter-evidence held on record
Counter-evidence The in vitro concentrations used in the class studies were not captured and may exceed what an oral 100 to 200 mg dose produces. Drug-induced mitochondrial effect at the dose range is therefore not demonstrated. The overdose literature describes toxicity through sodium channel blockade, not mitochondrial injury [8][9][10]. Framing caution Mechanistic curiosity only. Not a mitochondrial damage claim, not a deficiency, and not a reason to supplement CoQ10 or any other nutrient.
Oxidative Stress
Each finding below is counted once, in this area only.
Oxidative stress
Not graded — disclosed evidence gapSee study details
No benzonatate-specific evidence on redox or antioxidant markers was found, and the class items located do not support a claim for this drug.
Full detail and limits
Oxidative stress
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B source for benzonatate exists, and the Tier C items read ([21] amide agents under surgical confounding; [22] procaine abstract with unnamed markers) do not support a plausible, interpretable claim for an ester antitussive, so a yellow would not be defensible; and no circulating consumer claim of oxidative stress for benzonatate was found to rebut. This is a disclosed gap, not a finding of safety. Re-check when PubMed access is restored.
What was searched
Web search "benzonatate oxidative stress OR mitochondrial OR ATP cytotoxicity cells" (unrelated sodium benzoate and general toxicology records); "local anesthetic induced oxidative stress reactive oxygen species mitochondria review tetracaine"; "tetracaine OR procaine OR chloroprocaine reactive oxygen species lipid peroxidation antioxidant enzymes". Opened: a 2025 narrative review of regional anesthesia and oxidative stress biomarkers, which covers amide agents (bupivacaine, levobupivacaine, lidocaine) in surgical settings with mixed direction and no ester agents, tetracaine or benzonatate [21]; and the abstract of a 2012 physiotherapy-journal study of procaine in 90 subjects that says markers "normalize" without naming them or giving effect sizes [22]. The label has no oxidative stress statement [1]. Repair pass (2026-10-08): PubChem toxicity record for benzonatate (overdose course, case reports, HSDB, DILI classification) has no oxidative stress, antioxidant or redox content [30]; Bishop-Freeman 2017 abstract has none [31]. Planned PubMed, OpenAlex and Crossref searches for tetracaine, procaine or chloroprocaine with reactive oxygen species returned 429 or 404 and were not completed; MDPI and Frontiers site searches were blocked by robots rules or returned no results; the web search tool's per-turn budget was exhausted. No ester-anesthetic ROS paper was opened, so no yellow could be assigned.
Channel outcomes
Open web search plus publisher/repository fetches worked. PubMed listing: 404 then 429; PubMed and several PMC article pages: bot verification. A tooling-limited miss on the primary databases combined with a clean zero for benzonatate on open search. Judged a genuine gap in the literature for benzonatate itself, with a real tooling limit on the class (ester anesthetic) search; the repair pass could not complete it. Re-check with working PubMed access.
Copper and Iron Balance
Copper and iron are assessed separately. Nothing here is counted twice.
Copper
Not graded — disclosed evidence gapSee study details
No evidence connects benzonatate with copper status, absorption, chelation or excretion.
Full detail and limits
Copper
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C source and no circulating copper claim for benzonatate. Not a finding of safety. Kept independent of Iron (Hard Rule 7).
What was searched
Web search "benzonatate iron OR copper OR chelation OR anemia OR hemolysis" (results were Wilson disease and copper hemolysis papers with no benzonatate content); "does benzonatate deplete nutrients vitamins minerals drug-induced nutrient depletion" (generic depletion pages). Label sections on nutrients and interactions: nothing on copper [1]. A drug-interaction checker lists no food or mineral interactions [25]. A depletion chart (chiro.org) and a pharmacist depletion-checker page do not list benzonatate [27].
Channel outcomes
Open web and DailyMed worked. Primary database search was limited as described under Oxidative stress. No benzonatate metal-binding study was found. Repair pass: the PubChem toxicity record lists no nutrient or metal interactions and mentions magnesium only as prophylaxis in one overdose case report [30]; the PubChem interactions heading holds target tables only [DrugBank/DGIdb/DrugCentral/TTD links, not opened]. Genuine gap, with partial tooling limit.
Iron
Not graded — disclosed evidence gapSee study details
No evidence connects benzonatate with iron absorption, iron stores or iron-deficiency anemia.
Full detail and limits
Iron
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C source and no circulating iron claim for benzonatate. Any hemoglobin effect would belong to the oxygen delivery entry, where only a class-level methemoglobinemia flag exists. Not a finding of safety.
What was searched
The same combined iron/copper/anemia/hemolysis web query (no benzonatate content); the generic depletion queries; label review (no iron, anemia or hemolysis text) [1]; checker and chart pages [25][27]. The overdose case reports and series did not report ferritin or hemoglobin [7][8][9][10].
Channel outcomes
As for Copper. Repair pass: StatPearls methemoglobinemia chapter [29] and PubChem toxicity record [30] contain no benzonatate iron, anemia or hemolysis content; Bishop-Freeman 2017 [31] none. Genuine gap, with partial tooling limit.
Gut Microbiome Risk
Each finding below is counted once, in this area only.
Gut microbiome risk
Not graded — disclosed evidence gapSee study details
No study of benzonatate and the gut microbiome, fecal composition or C. difficile was located.
Full detail and limits
Gut microbiome risk
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C source opened that includes benzonatate or a class member, and no circulating microbiome claim. Not a finding of safety.
What was searched
Web search "benzonatate gut microbiome growth inhibition human gut bacteria drug screen" and "benzonatate gut microbiota OR microbiome OR fecal OR Clostridioides difficile OR dysbiosis" (results were sodium benzoate, C. difficile reviews and drug-screen papers without benzonatate). Opened the main text of Maier 2018 (1,197 drugs against 40 gut isolates): it does not mention benzonatate, tetracaine or other local anesthetics [23]. The screen's supplementary compound table was not opened, so inclusion of benzonatate in that screen is unknown. The label lists constipation, nausea and GI upset as adverse reactions [1], which are symptoms and not microbiome evidence.
Channel outcomes
Open web worked. Supplementary tables, PubMed listing, Europe PMC and Semantic Scholar were not available. Tooling-limited for the drug-screen supplement; otherwise a clean zero. Re-check the Maier 2018 supplement and any later non-antibiotic drug screens. Repair pass: the Nature article page [33] states the screen used the Prestwick Chemical Library (1,520 off-patent drugs) plus a Transbac library, and its supplementary table is linked only as an in-page anchor; the supplement file host disallows automated fetching by robots rules and was not accessed. The Prestwick vendor page does not list compound names [34]. Whether benzonatate is in the screen therefore remains unknown, and a growth-inhibition result for it, if present, would be Tier B in vitro data.
Oxygen and ATP Output
Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.
ATP production: class extrapolation, isolated ATPase inhibition by tetracaine
Yellow — LowSee study details
Tetracaine partially inhibits a mitochondrial ATPase preparation in the test tube. No study measured ATP synthesis, cellular ATP or energy output with benzonatate.
Full detail and limits
ATP production: class extrapolation, isolated ATPase inhibition by tetracaine
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow
Limits on what this shows
- Null findings: None located. A search for benzonatate with ATP, oxidative phosphorylation and cytotoxicity terms returned unrelated sodium benzoate and general toxicology records.
Regulatory status
Not mentioned in the benzonatate label [1].
Population evidence
None in humans or cells for benzonatate. Adade 1984 [18] (abstract only, read via a summarizing fetch): noncompetitive, partial inhibition of mitochondrial ATPase by tetracaine, lidocaine, dibucaine and chlorpromazine; benzocaine, a neutral anesthetic, inhibited at all pH values tested. Concentrations and the full text were not retrieved. ATP synthesis, ATP content and energy output were not measured in that abstract.
Mechanism
Named for tetracaine in a purified enzyme preparation only. Reduction of cellular ATP in a person taking benzonatate is not shown.
Class cohort test
CLASS EXTRAPOLATION. Benzonatate was not in the cohort. Tetracaine, a related ester anesthetic, was. Capped at yellow (Tier C). This entry shares its source with Mitochondrial burden (see Overlap map).
Counter-evidence held on record
Counter-evidence An isolated enzyme assay does not predict cellular ATP or fatigue in a patient. A "low energy" claim for benzonatate would have no support here, and none circulates. Framing caution Not an energy-loss claim and not a deficiency claim. Kept independent of Mitochondrial burden and Oxygen delivery/utilization (Hard Rule 7).
Oxygen delivery/utilization: methemoglobinemia as a local anesthetic class effect, not reported for benzonatate
Yellow — LowSee study details
Methemoglobinemia is a documented effect of some local anesthetics and is named in a tetracaine injection label, but benzonatate's own label does not mention it and no benzonatate case was found. Direction: oxidation of hemoglobin, an outcome rather than a nutrient.
Full detail and limits
Oxygen delivery/utilization: methemoglobinemia as a local anesthetic class effect, not reported for benzonatate
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow
Limits on what this shows
- Null findings: No benzonatate methemoglobinemia report surfaced in two benzonatate-specific web query phrasings or in the combined iron/anemia/hemolysis query (see Sources access note). Absence in a limited search is not proof of absence. Added in repair: the StatPearls methemoglobinemia chapter (updated December 2025) lists benzocaine, prilocaine, lidocaine and bupivacaine as local anesthetic causes and names neither benzonatate nor tetracaine [29]; the PubChem toxicity record for benzonatate does not discuss methemoglobinemia or any hematologic effect [30]; Bishop-Freeman 2017 (abstract via OpenAlex) discusses pharmacokinetics and toxicity of benzonatate and does not mention methemoglobin [31].
Regulatory status
Benzonatate label: methemoglobinemia not mentioned [1]. Tetracaine hydrochloride 1% injection label (a related ester anesthetic, Tier A for tetracaine): "Cases of methemoglobinemia have been reported in association with local anesthetic use" [14]. That statement is generic to the local anesthetic class and does not name benzonatate.
Population evidence
Guay 2009 [15] (abstract via reconstructed OpenAlex record; full text not opened): summary of 242 published local-anesthetic methemoglobinemia episodes, with pulse oximeter and PaO2 discrepancy in 91.8%; the abstract names benzocaine and prilocaine and does not name benzonatate or tetracaine. Narrative reviews and a case report of topical pharyngeal anesthesia identify benzocaine as the cause of most cases and call lidocaine-alone evidence insufficient [16][17]. A bronchoscopy case implicated lidocaine plus benzocaine, methemoglobin 17.5% [28]. Overdose case reports of benzonatate reported no methemoglobin measurement [9][10].
Mechanism
Plausibility for benzonatate is not established. The class link rests on shared local anesthetic status and the tetracaine label sentence. Which structural features drive methemoglobin formation in the implicated agents was not assessed from sources opened, so no mechanism is claimed for benzonatate.
Class cohort test
CLASS EXTRAPOLATION. Benzonatate was not identified in the cohort of any methemoglobinemia source opened ([14] names no agent; [15] abstract does not name benzonatate; [16][17][28] concern benzocaine, lidocaine). Whether benzonatate appears in the full text of [15] is unknown. Capped at yellow (Tier C).
Counter-evidence held on record
Counter-evidence and confounding The documented case series concentrate on topical sprays (benzocaine) and prilocaine at injection doses, a very different exposure from an oral capsule. Methemoglobinemia and cyanosis in an overdose would be confounded by arrest and hypoxia [10]. Framing caution Not a finding that benzonatate causes methemoglobinemia, and not an oxygen-carrying deficiency (Hard Rule 2). The label does not carry this warning. Do not present it as an expected effect.
Claims checked and not supported
These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.
A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.
None found (zero white entries)
Where it comes from: Checked for circulating nutrient-depletion claims: a drug-interaction checker (0 food interactions) [25], a patient-education page [26], a classic depletion chart and a pharmacist depletion-checker page [27], and generic web queries. The antidoteresearch.com benzonatate depletion URL returned 404. One consumer page (apollohospitals.com) returned 403 and was not read.
Why it fails: No page opened attributed any vitamin, mineral, antioxidant, mitochondrial, microbiome, oxygen-carrying or energy effect to benzonatate, so there is nothing to rebut. This table is empty by finding, not by omission. The only nutrient-adjacent consumer statement found, to avoid eating or drinking while the mouth is numb, is supported by the label and is handled under Dietary intake [1][26].
How the body handles this medication
- Metabolism and enzymes
- Hydrolyzed by plasma butyrylcholinesterase (BChE) to the major metabolite 4-(butylamino)benzoic acid (BABA). No CYP450 involvement is listed. The label itself does not describe metabolism. A secondary source adds that people with pseudocholinesterase deficiency may be more sensitive.[4][5][6] DrugBank via PubChem; Wikipedia (secondary); HPLC method for BABA in plasma. Label [1] silent.
- Elimination
- Not described in the label retrieved. A route of excretion and percent excreted unchanged were not found in any source opened. Whether benzonatate enters human milk is stated as unknown. The PubChem record quoting DrugBank states that information on volume of distribution, route of elimination and clearance is limited [32].[1][5][32]
- Absorption and onset
- The label's overdosage section says drugs of this type are generally well absorbed after ingestion. Onset is 15 to 20 minutes and duration about 3 to 8 hours. No transporter or site of absorption is named. A PubChem record quoting DrugBank reports gastrointestinal absorption with a peak concentration of 1063 +/- 460 ng/mL after a single 100 mg oral dose in healthy Chinese volunteers [32]. The capsule must be swallowed whole; release in the mouth produces temporary numbness and a choking risk.[1][3][32]
- Mechanism and target
- Anesthetizes stretch receptors in airways, lungs and pleura; no inhibition of the respiratory center at recommended doses. Described as a voltage-gated sodium channel inhibitor; DrugBank lists SCN5A as the target. Chemically related to procaine and tetracaine (PABA class).[1][4][5]
- Interactions
- The label has no dedicated interaction section and names no agents. A drug-interaction checker lists 2 drug interactions (tizanidine and tradipitant), 1 disease interaction (psychiatric conditions) and 0 food interactions. No mineral, vitamin or antacid interaction is documented.[1][25]
- Renal and hepatic impairment; special groups
- No renal or hepatic dosing statement appears in the label retrieved. Pediatric safety and effectiveness are not established under age 10, and accidental ingestion has caused death in children under 10. Pregnancy: no animal reproduction studies; give only if clearly needed. Maximum 200 mg per dose and 600 mg per day.[1][3]
What the research says is worth watching
General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.
Administration safety
Swallow capsules whole
Per the label, do not break, chew, dissolve or crush. If mouth, tongue, throat or face numbness or tingling occurs, avoid eating and drinking until it resolves, and seek care if it worsens or persists [1][3].
Poisoning
Overdose and accidental ingestion
Signs can appear within 15 to 20 minutes and deaths in children under 10 have followed accidental ingestion. This is an emergency for poison control or emergency care, not a nutrient matter. Keep capsules out of children's reach [1][3][11].
Lab / only if unexplained
Methemoglobin (co-oximetry)
Not a routine test for benzonatate. Co-oximetry is reasonable only if low pulse-oximeter readings occur without an explanation and normal arterial oxygen, particularly after other local anesthetic exposure. In the 242-episode review a pulse oximeter and PaO2 discrepancy was present in 91.8% of local-anesthetic episodes [15]. No benzonatate case is known from this review.
Nutrient labs
No routine nutrient monitoring
No vitamin, mineral or trace-element monitoring is supported by any source for benzonatate. Short-course use for cough is the label indication [1].
Timing
Supplement separation
No separation interval is required or documented for any vitamin, mineral or antacid [1][25]. No supplement dose is recommended or appears anywhere in this dossier, so no upper-limit comparison was needed.
Special populations
Pregnancy, pediatrics, other
Pregnancy: use only if clearly needed (no animal reproduction studies). Nursing: excretion in milk unknown. Under age 10: safety and effectiveness not established. A secondary source suggests pseudocholinesterase deficiency may raise sensitivity; this was not confirmed in the label [1][5]. Renal impairment was not addressed in the label retrieved.
Overlap map, to prevent double counting
Mitochondrial burden
Shares evidence with: ATP production
Note: Both rest on the same tetracaine ATPase abstract [18], with Mitochondrial burden adding the membrane-potential abstract [19] and review [20]. One class source, not two independent confirmations. Both are Tier C and capped at yellow.
Electrolytes in overdose
Shares evidence with: Dietary intake; Oxygen delivery/utilization
Note: The label [1] and FDA communication [3] appear in the intake and overdose entries for different statements (swallow whole and numbness versus overdose course). Case reports [9][10] appear in the electrolyte entry and as a null (no methemoglobin measured) in the oxygen entry. Same papers, different questions.
Oxygen delivery/utilization
Shares evidence with: Iron (ungraded)
Note: Any hemoglobin or red-cell effect would run through these two entries; none is double-counted. Methemoglobinemia is an oxidation outcome, not an iron or ATP finding.
Oxidative stress (ungraded)
Shares evidence with: Mitochondrial burden
Note: No shared evidence is used. Mitochondrial inhibition could in theory raise reactive oxygen species, but no source tested it for benzonatate or tetracaine, so none is claimed.
Copper
Shares evidence with: Iron
Note: No shared source. Both are ungraded after the same combined query and label review; graded as two separate entries per Hard Rule 7.
Gut microbiome risk
Shares evidence with: None
Note: No source in common with any other entry.
All references used above
- Benzonatate 100 mg and 200 mg capsules, prescribing information (DailyMed, Marksans Pharma Limited). — Regulatory label (Tier A). Read through a summarizing fetch tool, not directly. Revision date not captured. Description, clinical pharmacology, warnings, precautions, adverse reactions, overdosage, pregnancy, pediatric sections.One generic labeler's label of 174 listed; other labelers were not compared.
- WHO Collaborating Centre, ATC/DDD Index: benzonatate, R05DB01 (Other cough suppressants). — Reference index.
- FDA Drug Safety Communication, December 14, 2010: death resulting from overdose after accidental ingestion of Tessalon (benzonatate). — Regulatory communication (Tier A). 31 overdose cases through May 19, 2010; 7 accidental pediatric ingestions, 5 fatal; swallow-whole and numbness/choking instructions. Read through a summarizing fetch tool.
- DrugBank DB00868 (benzonatate) and PubChem CID 7699 metabolism/metabolites section. — Database references (Tier B for established pharmacology). Source of BChE hydrolysis to BABA (PubChem quoting DrugBank), sodium channel inhibitor description, SCN5A target. DrugBank absorption, half-life, elimination and protein binding were behind a sign-in and not retrieved. A PubChem absorption/excretion lookup returned 429.
- Wikipedia, Benzonatate. — Secondary reference, not used as evidence for any grade. Used for brand names, BChE hydrolysis (consistent with [4]), pseudocholinesterase deficiency remark and PABA-class description. Its cited references were not opened (Dicpinigaitis 2009 and Bishop-Freeman 2017 among them).
- Lin W-J, Chen RR-L, Suen S-L. Determination of benzonatate and its metabolite in plasma by high performance liquid chromatography. Chin Pharm J 1996;48(1):53-61. — HPLC method plus preliminary pharmacokinetics of 4-(butylamino)benzoic acid in healthy male volunteers. Abstract only, via the NTU repository page.
- Winter ML, Spiller HA, Griffith JRK. Benzonatate ingestion reported to the National Poison Data System. J Med Toxicol 2010;6(4):398-402. — Retrospective poison-center review, 2,172 single-substance ingestions, 2000 to 2006. Read at PMC (via summarizing fetch).
- Minhaj FS, Leonard JB. A description of the clinical course of severe benzonatate poisonings reported in the literature and to NPDS: a systematic review supplemented with NPDS cases. Hum Exp Toxicol 2021;40(12 suppl):S39-S48. — Systematic review, 36 cases (17 NPDS, 19 published). PMID 34219543. Abstract read through a reconstructed OpenAlex record and a summarized PubMed page; full text not opened.
- Jin C, Zahid E, Sherazi A, Majumder MR, Bedi P. Cardiac arrest due to benzonatate overdose. Am J Case Rep 2019;20:640-642. — Single case report. DOI 10.12659/AJCR.915151. Read via summarizing fetch of the journal page and PMC copy.
- Billington M, Furmaga J, Schaeffer T. Arrhythmogenic antitussive: a case of pediatric benzonatate overdose with torsades de pointes, cardiac arrest, and complete recovery without neurologic deficits. J Pediatr Pharmacol Ther 2020;25(7):642-646. — Single case report, n=1. DOI 10.5863/1551-6776-25.7.642. Read via summarizing fetch of PMC.
- Benzonatate exposure trends and adverse events. Pediatrics 2022 (authors not shown on the page retrieved). — Retrospective analysis of dispensing, poison-center, injury surveillance and FDA data; 4,689 pediatric exposures 2010 to 2018, 77% unintentional. Abstract only, via a QxMD listing.
- Costantino RC, Leonard JB, Gorman EF, Ventura D, Baltz A, Gressler LE. Benzonatate safety and effectiveness: a systematic review of the literature. Ann Pharmacother 2023;57(10):1221-1236. — Systematic review, 37 articles (21 cohort, 5 experimental, 11 case reports/series), high risk of bias. PMID 36688284. Abstract only, via OpenAlex (paraphrased by the fetch tool).
- emDocs. ToxCard: benzonatate (January 2024). — Educational summary (Tier D for evidence). Used only to cross-check the toxicity picture and to locate primary references; nothing graded rests on it.
- Tetracaine hydrochloride 1% injection (spinal), prescribing information, Rev. 03/2020, as shown on Drugs.com (page updated January 4, 2026). — Regulatory label for a related ester anesthetic (Tier A for tetracaine only). Warnings: "Cases of methemoglobinemia have been reported in association with local anesthetic use." Read through a summarizing fetch tool.Cohort excluded benzonatate: label of a different drug. Class extrapolation only.
- Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth Analg 2009;108(3):837-845. — Literature summary of case episodes. PMID 19224791; DOI 10.1213/ane.0b013e318187c4b1. Abstract read via a reconstructed OpenAlex record; the PubMed page returned bot verification; full text not opened.Benzonatate not named in the abstract; inclusion in the full text unknown. Tier C for this drug.
- Vallurupalli S. Methemoglobinemia due to topical pharyngeal anesthesia during endoscopic procedures. Local Reg Anesth 2010;3:137-142. — Narrative review. Page content names benzocaine only.Excluded cohort: benzonatate not mentioned.
- Riaz S, Kudaravalli P, Saleem SA, Heisig D. Methemoglobinemia: a life-threatening complication of topical pharyngeal anesthetics. Cureus 2020 (journal inferred from DOI 10.7759/cureus.7900). — Single case report (benzocaine, 22-year-old). States lidocaine-alone evidence is insufficient. Tetracaine and benzonatate not mentioned.Excluded cohort: benzonatate not studied.
- Adade AB, Chignell D, Vanderkooi G. Local anesthetics: a new class of partial inhibitors of mitochondrial ATPase. J Bioenerg Biomembr 1984;16:353-363. — In vitro enzyme study; tetracaine, lidocaine, dibucaine, chlorpromazine (noncompetitive, partial inhibition) and benzocaine. Abstract only via a summarizing fetch.Excluded cohort: benzonatate not tested. Tier C for this drug.
- Grouselle M, Tueux O, Dabadie P, Georgescaud D, Mazat JP. Effect of local anaesthetics on mitochondrial membrane potential in living cells. Biochem J 1990;271(1):269-272. — Cell study (rhodamine 123). Abstract only; agents tested and concentrations not captured.Cohort not verified; benzonatate presumed not tested. Tier C for this drug.
- Shen X, et al. Is cardiolipin the target of local anesthetic cardiotoxicity? Rev Bras Anestesiol 2010;60(4). — Hypothesis review; amide agents mainly. Benzonatate does not appear in the text.Excluded cohort: benzonatate not discussed.
- Jaruga K, Puscion-Jakubik A, Jakubow P. Regional anesthesia: a narrative review of impact on oxidative stress biomarkers. Journal named as likely J Clin Med 2025 (from table labels). — Narrative review; amide agents only.Excluded cohort: benzonatate and ester agents absent.
- Turova EA, Konchugova TV, Balaban EI, et al. The influence of procaine on the parameters of lipid peroxidation and antioxidative protective system. Russ J Physiother Balneol Rehabil 2012;11(5):41-43. — Abstract only; 90 subjects; procaine by electrophoresis or mesotherapy; markers unnamed.Excluded cohort: procaine only, not benzonatate.
- Maier L, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 2018. — In vitro screen, 1,197 drugs against 40 gut isolates. Main text read from a hosted PDF; benzonatate not mentioned; supplementary tables not opened.
- Sulica L, Hembree A, Blitzer A. Swallowing and sensation: evaluation of deglutition in the anesthetized larynx. Ann Otol Rhinol Laryngol 2002;111(4):291-294. — Experimental study, 5 healthy adults, laryngeal nerve block. Abstract only.Excluded cohort: nerve block, not benzonatate. Context only.
- Drugs.com. Benzonatate drug interactions page. — Tier D for evidence; used to confirm 2 drug, 1 disease and 0 food interactions listed.
- Memorial Sloan Kettering Cancer Center. Benzonatate (adult patient education). — Tier D; circulating-guidance check. Eating/drinking and swallow-whole instructions; no nutrient claims.
- Drug-nutrient depletion and interaction charts (chiro.org) and Hello Pharmacist nutrient depletion checker. — Tier D; circulating-claim check only. Neither lists benzonatate (the second showed only a partial directory preview).
- Case report of methemoglobinemia during bronchoscopy with lidocaine and benzocaine (62-year-old man), J Med Case Reports 2008. — Single case; methemoglobin 17.5%. Title, authors and journal not shown on the page retrieved; journal and year inferred from the URL path (10.1186/1752-1947-2-16).Excluded cohort: benzonatate not involved.
- StatPearls. Methemoglobinemia (NCBI Bookshelf NBK537317, updated December 14, 2025). — Reference chapter (Tier B for established pharmacology). Etiology section names benzocaine, prilocaine, lidocaine and bupivacaine among local anesthetic causes; benzonatate and tetracaine are not named. Read through a summarizing fetch tool. Used as a null finding only.Benzonatate absent. Added in repair pass 2026-10-08.
- PubChem CID 7699 (benzonatate), Toxicity heading, aggregating DailyMed, HSDB, LactMed and FDA LTKB records. — Database record (Tier B). Overdose course, two case reports (Crouch 1998 PMID 9865240; Cohen 2011 PMID 19892505, not opened individually), DILI classifications that disagree. No methemoglobinemia, hematologic, oxidative stress or nutrient and metal content. Read through a summarizing fetch tool.Added in repair pass 2026-10-08. Null-finding use only.
- Bishop-Freeman SC, Shonsey EM, Friederich LW, Beuhler MC, Winecker RE. Benzonatate toxicity: nothing to cough at. J Anal Toxicol 2017;41(5):461-463. DOI 10.1093/jat/bkx021; PMID 28334901. — Letter on benzonatate toxicity and pharmacokinetics; parent drug not detected in one case, metabolite BABA identified, suggesting hydrolysis; pseudocholinesterase deficiency may prolong activity. Abstract read via a paraphrasing fetch of the OpenAlex record; full text not opened. No nutrient, electrolyte, methemoglobin, iron or copper content in what was read.Full text not opened. Added in repair pass 2026-10-08.
- PubChem CID 7699 (benzonatate), Absorption, Distribution and Excretion heading, quoting DrugBank DB00868. — Database record (Tier B). Cmax 1063 +/- 460 ng/mL after a 100 mg oral dose in healthy Chinese volunteers; volume of distribution, elimination route and clearance described as limited. Read through a summarizing fetch tool.Added in repair pass 2026-10-08.
- Maier L, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 2018 (journal article page). — Page opened for library description (Prestwick Chemical Library, Transbac library) and supplementary table links. Benzonatate and local anesthetics are not mentioned on the page; the supplementary file was not accessed.Supplement not opened (host disallows automated fetching). Added in repair pass 2026-10-08.
- Prestwick Chemical Library, vendor description page. — Describes 1,520 off-patent drugs; compound names are not listed on the page and no downloadable list is offered. Tier D for evidence; used only to document the access attempt.Added in repair pass 2026-10-08.