BENZONATATE (Generic for TESSALON PERLE)

Benzonatate is an oral nonnarcotic antitussive agent that is chemically related to tetracaine and other ester-type local anesthetics. Historically, benzonatate has been used to suppress cough associated with acute respiratory conditions like colds and other respiratory tract infections. While benzonatate has been in use as an antitussive for decades, controlled trials are not available to support the efficacy of the drug when compared to placebo or other antitussive medications; guidelines designate benzonatate as an agent of limited utility. Case reports suggest that benzonatate might be helpful to palliate chronic cough not responding to opiate agonists, particularly in patients with advanced cancer, but supportive data are limited. Although not FDA-approved for this purpose, benzonatate has been applied topically to the oropharynx to obliterate the gag reflex prior to intubation or endoscopy. Tessalon(R) Perles have also been applied externally to areas of the body prior to magnetic resonance imaging (MRI). This unusual use is unrelated to the pharmacology of the medication. The three-dimensional capsules are good sources of multiple protons and show up well as 'markers' on the MRI image for more accurate mapping and measurement of defined lesions or abnormalities. Benzonatate was approved by the FDA in 1958.

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
Oral Solid Formulations
-Swallow whole. Do not break, chew, or dissolve in the mouth as this could cause temporary anesthesia of the mouth and throat and could cause choking.

In general, benzonatate is typically well tolerated. Mild gastrointestinal upset, constipation, and nausea have been reported.

Benzonatate is related to the ester-type local anesthetics and severe hypersensitivity reactions including anaphylactoid reactions, bronchospasm, hypotension, or laryngospasm may occur. Cardiovascular collapse may be possibly related to local anesthesia from chewing or sucking the capsule. Severe reactions have required intervention with vasopressor agents and supportive measures. If benzonatate is chewed or dissolved in the mouth, dysphagia and oropharyngeal anesthesia will develop rapidly and may result in choking or a compromised airway. Dermatologic effects have included pruritus and rash (unspecified).

In general, benzonatate is typically well tolerated. Among the most common reported side effects are sedation (drowsiness), mild dizziness, and headache. Like other local anesthetics, it is sometimes associated with mental confusion, visual hallucinations, or other strange behaviors.

Rare and isolated side effects reported with the use of benzonatate include nasal congestion, ocular irritation (burning sensation), vague reports of chills, and "numbness" of the chest.

Benzonatate is chemically related to tetracaine and other ester-type local anesthetics. Use of benzonatate is contraindicated in those patients with ester local anesthetic hypersensitivity or a previous history of reaction to benzonatate. The benzonatate formulation also contains methyl- and propylparaben; these may be a problem for patients with paraben hypersensitivity. Severe hypersensitivity reactions have been reported with benzonatate use. In some cases local anesthesia resulting from the sucking or chewing of the capsule has been responsible for bronchospasm or laryngospasm. Patients should always swallow benzonatate capsules whole, do not chew or dissolve in the mouth.

Children 10 years of age or older may receive benzonatate with careful administration instructions to avoid chewing or dissolving the dose in the mouth. Safe and effective use of benzonatate has not been established in neonates, infants, or children under the age of 10 years. Accidental ingestion of benzonatate liquid capsules poses a significant potential for overdose or poisoning to pediatric patients younger than 10 years of age due in part to the candy-like appearance. Signs and symptoms of overdose have been reported within 15 to 20 minutes, and death has been reported within one hour of ingestion. Advise patients to store this medication out of reach of children in a child-resistant container and to seek medical help immediately if accidental ingestion is suspected. The Adverse Event Reporting System database of the FDA includes 7 cases of accidental pediatric exposure reported between 1982 and May 2010, including 5 deaths in children less than 2 years of age. Overdose has occurred in children under 2 years after accidental ingestion of one or two benzonatate capsules. In addition, the benzonatate dosage form could represent a choking hazard to young children.

Benzonatate is occasionally associated with CNS sedation, mental confusion, visual hallucinations or other bizarre behaviors. Patients should be advised to use caution with driving or operating machinery or performing other activities requiring mental alertness until they know how this medication affects them. Concomitant medications could increase the risk of these types of adverse reactions.

Benzonatate is classified as FDA pregnancy risk category C. Animal studies to evaluate carcinogenic and mutagenic potential and effect on gestation and fertility have not been performed. Due to a lack of available data on the safety of benzonatate during pregnancy, the drug should be administered to a pregnant woman only if clearly needed. The effects of benzonatate during labor and obstetric delivery are unknown. However, benzonatate is chemically related to anesthetic agents such as procaine and similar effects could be observed if enough absorption takes place. Local anesthetics rapidly cross the placenta and can cause varying degrees of maternal, fetal, and neonatal toxicity when used for paracervical or pudendal block anesthesia during labor and delivery. The use of some local anesthetics during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life in the newborn. The long-term significance of these observations is unknown.

According to the manufacturer, it is not known if benzonatate is excreted in human milk, and caution is recommended if the drug is used during breast-feeding. The effects of benzonatate on a nursing infant are unknown, and the American Academy of Pediatrics (AAP) has not issued any specific recommendations relating to benzonatate and breast-feeding. Because no breast-feeding information is available, an alternate anti-tussive may be preferred, especially while nursing a newborn or premature infant. Despite the lack of published data, some experts consider dextromethorphan to be compatible with breast-feeding when usual adult doses are taken by the mother. Dextromethorphan products containing alcohol should be avoided. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Cautious use of benzonatate may be warranted for patients with para-aminobenzoic acid, PABA hypersensitivity. Benzonatate is chemically related to anesthetic agents of the para-aminobenzoic acid class such as procaine and tetracaine. Benzonatate has been associated with adverse CNS effects possibly related to a prior sensitivity to related agents or to an interaction with concomitant medication.

Geriatric patients taking benzonatate should be able to swallow the capsules as directed, as inadvertant release of capsule contents in the mouth can produce a temporary local anesthesia of the oral mucosa and choking or other serious side effects could occur. The medication is advised to be avoided if dysphagia is present. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. According to the OBRA guidelines, cough medications should be used only for a limited duration (less than 14 days) unless there is documented evidence of enduring symptoms that cannot otherwise be alleviated and for which a cause cannot be identified and corrected.

For the symptomatic treatment of cough:
Oral dosage:
Adults, Adolescents and Children 10 years and older: 100 mg, 150 mg, or 200 mg PO 3 times daily is the normal dosage. Maximum dosage is 600 mg/day PO.

For the treatment of intractable singultus (hiccups)* unresponsive to standard therapies:
Oral dosage:
Adults, Adolescents and Children 10 years and older: Anecdotal reports suggest a dosage of 100 mg PO as a single dose. May repeat in 4 hours if needed. Dose of 100 mg PO may be given up to every 4 hours; do not exceed 600 mg/day PO.
Children younger than 10 years: Safe and effective use is not established.

For topical anesthesia* of the oropharyngeal region prior to awake endotracheal intubation* or prior to endoscopy*:
NOTE: This route should only be used by health care professionals trained in anesthesia and intubation. Specialized references should be consulted for specific procedures and administration techniques. Resuscitative equipment and drugs used in the management of adverse reactions should be immediately available.
Oropharyngeal topical dosage*:
Adults: A dose of 200 mg applied topically to the oropharyngeal area, followed by 4% lidocaine translaryngeally has been used. This route should only be used by those trained in anesthesia and intubation. In 1 study, a shorter time period was required to obtain the loss of gag reflex in the benzonatate-treated group (i.e., roughly 1 minute) vs. the 5 to 6 minutes required in those patients receiving superior laryngeal nerve block with 1% lidocaine.
Children: Safe and effective use is not established.

Maximum Dosage Limits:
-Adults
600 mg/day PO.
-Geriatric
600 mg/day PO.
-Adolescents
600 mg/day PO.
-Children
10 years and older: 600 mg/day PO.
9 years and younger: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

There are no drug interactions associated with Benzonatate products.

Benzonatate acts peripherally by anesthetizing the stretch receptors of vagal afferent fibers located in the alveoli of the lungs, the bronchi, and the pleura. The drug may also act centrally by inhibiting the transmission of the cough reflex at the level of the medulla where the vagal afferent impulse is transmitted to the motor nerves. In patients with asthma, intravenously administered benzonatate increased minute ventilation, rate and depth of respiration. However, overall lung volume and expiratory flow rate were not altered. At recommended oral dosages, benzonatate has no inhibitory effect on the respiratory center; however, in overdosage, the pharmacology of benzonatate resembles that of other ester-type local anesthetics. Clinical effects include initial CNS stimulation, which is followed by CNS depression and respiratory compromise.

When applied locally, as in the oropharynx prior to intubation or endoscopy, benzonatate acts like other local anesthetics. The drug blocks the generation and conduction of nerve impulses at the level of the cell membrane. Local anesthetics bind directly within the intracellular portion of voltage-gated sodium channels. This decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. The blockade affects all nerve fibers in the following sequence: autonomic, sensory, and motor, with effects diminishing in reverse order. Loss of nerve function clinically is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone. Direct nerve membrane penetration is necessary for effective anesthesia, which is achieved by applying benzonatate around the nerve trunks or ganglia supplying the area to be anesthetized. Benzonatate provides anesthesia in roughly 1-2 minutes after direct topical application to the oropharynx, noticeable clinically as the loss of the gag reflex.

Benzonatate is usually administered orally. The onset of action is 15 to 20 minutes, and antitussive effects last for approximately 3-8 hours. It is assumed that benzonatate, like other ester-type local anesthetics, is hydrolyzed to para-aminobenzoic acid (PABA) by plasma esterases. However, the absorption, distribution, metabolism and excretion of benzonatate are not well characterized.