Benzonatate
Benzonatate
Generic Name
Benzonatate
Mechanism
- Peripheral local anesthetic: Benzonatate is a *n-prenylated* analog of *procaine* that afflicts voltage‑sensitive sodium channels in the sensory nerves of the trachea, bronchi, and pharynx.
- Epsilon‑ketamine‑like binding: It blocks the influx of Na⁺ ions, stabilizes neuronal membranes, and *decreases afferent reflex activity* that would otherwise trigger cough reflex arcs.
- Minimal central nervous system penetration: Because it is poorly lipophilic, it is largely confined to the peripheral airway, reducing the risk of respiratory depression seen with opioid cough suppressants.
Pharmacokinetics
| Parameter | Description |
| Absorption | Oral tablets are *slowly* absorbed; peak plasma concentrations occur 1–2 h post‑dose. |
| Bioavailability | Approximately 5–10 % due to extensive first‑pass hydrolysis. |
| Distribution | Widely distributed; ~80 % protein bound (primarily to albumin). High tissue penetration into the respiratory mucosa. |
| Metabolism | Cleaved by plasma and tissue carboxylesterases to 1‑(3‑propyl)‑2‑pyrrolidine‐4‑acetic acid (inactive). No significant CYP450 involvement. |
| Elimination | Renally excreted as metabolites; *half‑life* of ~3–4 h. |
Indications
- Acute cough due to upper respiratory tract infections, cold, flu, or non‑specific bronchitis.
- Chronic cough (e.g., post‑viral, smokers’ cough) refractory to antitussive therapy.
- Adjunctive therapy for difficulty clearing secretions post‑surgery or in chronic pulmonary disease when limiting coughing is desired.
*It is not indicated** for cough associated with asthma exacerbations, or when the cough is a symptom of wheeze or dyspnea.*
Contraindications
- Hypersensitivity to benzocaine, procaine, or other local anesthetics.
- Concurrent use of other local anesthetic agents that may increase systemic toxicity.
- Children under 5 years: these age groups are most at risk for local anesthetic systemic toxicity (LAST) if capsules are mishandled; the FDA limits usage to ≥5 years.
- Pregnancy/Breastfeeding: Limited data; generally avoided unless benefits outweigh risks.
- Seizure disorders: Risk of provoking seizures from systemic absorption.
- Ingestion of capsule pieces: May lead to systemic toxicity; caution with chewing or splitting tablets.
Warnings
• Because benzonatate contains a local anesthetic moiety, ingestion or accidental swallowing of broken capsules can produce symptoms of LAST: tremor, seizures, arrhythmia, hypotension.
• Use with caution in patients with hepatic impairment or renal insufficiency (metabolism and excretion may be altered).
Dosing
| Population | Adult Dose | Pediatric Dose (5–12 yrs) | Pediatric Dose (≥13 yrs) |
| Oral capsules | 100 mg in the morning, 200 mg in the afternoon, 100 mg before bedtime (max 1 tablet × 3). | 10 mg/kg (up to 200 mg) per dose, 2–3 times daily. | |
| Administration | Take whole capsule with a full glass of water. Do not chew or split. | Follow same instructions; can take with food to reduce GI upset. |
• Adjust doses for renal/hepatic impairment as clinically warranted.
• Titration may be performed to achieve desired cough suppression while monitoring for signs of toxicity.
Adverse Effects
| Common (≤5 %) | Serious (≤1 %) | |
| Mild dizziness, drowsiness, tingling in lips/cheeks | Local anesthetic systemic toxicity: seizures, arrhythmia, severe hypotension | |
| Nausea, vomiting, mild GI discomfort | Hypotension, bronchospasm (rare) | |
| Headache, flushing | Pulmonary edema (very rare) | |
| Dry mouth | Allergic reaction: rash, urticaria, anaphylaxis |
• Serious adverse effects typically occur when capsules are accidentally ingested in a non‑professional manner (chewed, crushed) or in overdose.
Monitoring
1. Vital signs: BP, HR, RR, temperature before first dose and upon any change in clinical status.
2. Signs of LAST: tremor, blurred vision, tinnitus, seizures.
3. Renal function: serum creatinine and eGFR for patients on higher doses or with chronic kidney disease.
4. Toxicity assessment: Ingestion of capsule fragments or patient reporting loss of consciousness.
• In case of suspected toxicity, immediate airway, breathing, circulation (ABC) stabilization and consultation with an emergency department.
Clinical Pearls
- Never split or chew a benzocaine‑based capsule—local anesthetic toxicity is dose‑dependent on the amount of exposed drug.
- Keep away from young children; store in a child‑proof container to avoid accidental ingestion.
- Digital adhesive tapes or syringe pumps are not recommended, as the capsules are the only approved formulation.
- Screen for concurrent use of other anesthetic agents (e.g., lidocaine) and avoid stacking of local anesthetics.
- Patient education: Inform patients that cough suppression will *not* relieve expectoration; they may need to proceed with other therapies (e.g., mucolytics) to clear secretions.
- Renal impairment: While metabolism is primarily hydrolytic, decreased excretion of inactive metabolites can raise plasma levels; dose adjustment may be prudent.
- In overdose or LAST: Treat with *water‑soluble local anesthetic antagonists?* (No specific antidote; supportive care + benzodiazepines for seizures).
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• Benzonatate offers a targeted, peripheral antitussive effect without the respiratory depressant risks of opiates, making it a valuable adjunct in cough management when used correctly and with patient safety monitoring.