Benzocaine
Benzocaine is a short-acting local anesthetic of the ester type. It is used for topical anesthesia in a wide variety of clinical situations including mucous membrane anesthesia prior to endoscopic examination or instrumentation, gag reflex suppression, anorectal disorders, and various pain syndromes. It is available in many dosage forms including gels, creams, ointments, lotions, aerosols, and lozenges. In 2006, the Veterans Health Administration announced the decision to stop using benzocaine sprays in procedures that require tube insertion in the larynx or pharynx or in minor surgical procedures performed in these locations; other benzocaine products and benzocaine sprays applied to exterior skin are still allowable. The removal of benzocaine sprays used in the mouth and throat from practice is based on the belief that other topical anesthetics are less likely to cause methemoglobinemia. Further, tube insertion or surgical procedures in the larynx or pharynx might cause similar signs of methemoglobinemia, which may mean that methemoglobinemia may go unrecognized in some cases. Many over-the-counter (OTC) products are available for the temporary relief of dental or oral pain. OTC benzocaine products should not be used for teething pain and are contraindicated in infants and children younger than 2 years of age, due to the risk of methemoglobinemia. These products should also be used sparingly and not applied more frequently than 4 times per day in older pediatric patients and adults.Food and Drug Administration. FDA Drug Safety Communication: Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics. Benzocaine and tetracaine are more likely to cause contact sensitization than are other local anesthetics.
Lidocaine
Lidocaine is a widely used antiarrhythmic and amide-type local anesthetic. As an anesthetic agent, it is available as an ointment, jelly, patch, or aerosol for topical use, as an oral solution, and as an injection. Lidocaine is classified as a class Ib antiarrhythmic. It may be considered for ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) that is unresponsive to cardiopulmonary resuscitation (CPR), defibrillation, and vasopressor therapy. Evidence is inadequate regarding the routine use of lidocaine after cardiac arrest or early (within the first hour) after return of spontaneous circulation (ROSC). However, prophylactic use of lidocaine may be considered in certain circumstances (e.g., during emergency medical services transport) when treatment of recurrent VF/pVT may be challenging.Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S444-64. Panchal AR, Berg KM, Kudenchuk PJ, et al. 2018 American Heart Association focused update on advanced cardiovascular life support use of antiarrhythmic drugs during and immediately after cardiac arrest: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2018;138:e740-e749. Panchal AR, Bartos JA, Cabanas JG, et al. Part 3: Adult Basic and Advanced Cardiovascular Life Support: 2020 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142:S366-S468. Due to the potential for serious adverse reactions, including cardiovascular depression, continuous electrocardiogram monitoring is recommended during intravenous lidocaine treatment.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.
Phenylephrine HCl
Phenylephrine is a synthetic sympathomimetic amine with selectivity for the alpha-1-adrenergic receptor. Phenylephrine lacks significant inotropic and chronotropic effectsPhenylephrine hydrochloride injection package insert. Lake Forest, IL: Hospira, Inc.; 2005 Nov. Phenylephrine is used orally and intranasally to treat nasal congestion. Use in younger children has been associated with an increased risk of serious adverse effects; as a result, the FDA issued a public health advisory recommending that OTC cough and cold products not be used in infants and children < 2 years of age.Centers for Disease Control and Prevention (CDC). Infant deaths associated with cough and cold medications – two states, 2005. MMWR Weekly 2007;56:1-4. Parenterally, phenylephrine may reduce heart rate and cardiac output as a reflex response to its potent vasopressor effects, which is the rationale for its use to treat paroxysmal supraventricular tachycardia. Since it is a potent vasoconstrictor, phenylephrine injection can be used as a vasopressor; however the predominance of alpha-effects and lack of beta-1 inotropic effects limits the use of phenylephrine for the treatment of shock states. Phenylephrine injection was FDA-approved in December 2012.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun.
Prilocaine
Prilocaine hydrochloride is a local anesthetic of the amide class used primarily for dental anesthesia. It has an intermediate duration of action and is longer acting than lidocaine. Prilocaine produces less vasodilation than do equal amounts of lidocaine. Prilocaine was approved by the FDA in 1965.
Tetracaine
Tetracaine is an ester-type local anesthetic with an intermediate to long duration of action. Relative to other local anesthetics, tetracaine in considered the most toxic. Tetracaine is available in various injectable forms for spinal anesthesia, as well as preparations for topical use. These preparations are typically used prior to examination of the larynx, trachea, or esophagus, to abolish laryngeal and esophageal reflexes and provide local analgesia. Topical nonprescription products are also available for the temporary relief of pain associated with herpes labialis. Tetracaine received FDA approval in 1965.
Benzocaine
Do not use benzocaine 72 hours before having pancreatic function tests with bentiromide because this could interfere with results.
Prolonged use of topical anesthetics is not recommended. Preparations should not be used for more than 2 days without consulting the physician. Applying topical benzocaine preparations to severely traumatized skin (e.g., skin abrasion, eczema, burns), to large surface areas, or to warm skin (i.e., after exercise or application of thermal heat wraps or heating pads) can increase its absorption, possibly increasing the risk of systemic toxicity. Also, applying large amounts of benzocaine or using an occlusive dressing (skin wraps) can increase benzocaine absorption. At least 2 reports of deaths exist after application of topical anesthetics prior to cosmetic procedures. In both instances, women, aged 22 and 25 years, applied topical anesthetics to their legs and wrapped the treated area, as directed, in plastic wrap to enhance the numbing effect of the cream. Both women died from toxic effects of the topical anesthetic. The preparations used in both cases were compounded in pharmacies and contained high amounts of lidocaine and tetracaine. In order to reduce the risk of toxicity due to increased absorption of topical anesthetic, the FDA recommends patients use a topical anesthetic containing the lowest amount of medication needed to relieve pain, apply the medication sparingly. and only treat known or anticipated areas of pain. Further, do not apply the anesthetic to broken or irritated skin, be aware of potential adverse reactions, and do not cover or apply heat to the treated area.
Benzocaine can mask the symptoms of acute otitis media infection and should be used with caution in patients with otic pain syndromes. Do not use in patients who have a tympanic membrane perforation or unexplained ear discharge.
Benzocaine is a local ester anesthetic and should not be used in those with ester local anesthetic hypersensitivity. Also, ester-type local anesthetics such as benzocaine are metabolized to para-aminobenzoic acid (PABA) and should not be used in patients with para-aminobenzoic acid, PABA hypersensitivity. Some preparations contain tartrazine, which can cause allergic reactions and bronchospasm in susceptible individuals. Although the overall incidence of tartrazine dye hypersensitivity is low, it occurs more frequently in patients with aspirin sensitivity. Further, some preparations contain parabens, and cautious use of these preparations in patients with paraben hypersensitivity is warranted. The Kank-A SoftBrush product contains butylparaben, ethylparaben, methylparaben, and propylparaben.
It is not known whether benzocaine is excreted in human breast milk, however in general, topically applied benzocaine is unlikely to affect the nursing infant if it is applied away from the breast. Benzocaine has been associated with life-threatening cases of methemoglobin; products should be applied and used only as directed and the drug should never be applied to the breast or nipple in order to avoid infant ingestion.FDA Drug Safety Communication: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth. Retrieved April 7, 2011. Benzocaine was not evaluated by previous American Academy of Pediatrics (AAP) recommendations; however, the recommendations considered lidocaine as usually compatible with breastfeeding.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.
Geriatric patients and those with hepatic disease; cardiac disease or shock; endocrine diseases such as hyperthyroidism, diabetes mellitus, or Graves’ disease; or CNS disease are at an increased risk of developing benzocaine-related adverse effects. Benzocaine use can result in potentially dangerous levels of methemoglobinemia. Patients with reduced oxygenation status may have signs and symptoms of methemoglobinemia at lower serum methemoglobin concentrations than healthy individuals. Patients with breathing problems such as those with asthma, bronchitis, emphysema, chronic obstructive pulmonary disease (COPD), or cardiac disease, tobacco smoking patients, and the elderly are at greater risk for complications related to methemoglobinemia. Patients with certain hereditary defects including G6PD deficiency, hemoglobin-M disease, methemoglobin reductase deficiency, and pyruvate-kinase deficiency may also be at greater risk for developing methemoglobinemia.Food and Drug Administration. FDA Drug Safety Communication: Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics. These patients may have an absence or reduced level of enzymes that help reverse methemoglobinemia. OTC benzocaine products should be used sparingly and only as needed; do not apply more frequently than 4 times per day. Signs and symptoms of methemoglobinemia may appear within minutes to 1 to 2 hours after benzocaine exposure and may occur with initial and/or subsequent use. Advise patients to seek immediate medical attention for discoloration (pale, gray, or blue-colored) of skin, lips, or nail beds; shortness of breath; fatigue; confusion; headache; lightheadedness; or rapid heart rate. Health care professionals using local anesthetics during medical procedures should monitor patients closely for methemoglobinemia, use co-oximetry when possible (methemoglobinemia can cause unreliable readings on standard two-wavelength pulse oximeters), and have resuscitation equipment and medications readily available, including methylene blue.Food and Drug Administration. FDA Drug Safety Communication: Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics. Several factors influence the amount of benzocaine contained in a single spray including manufacturer differences, varying concentrations, length of time actuator is depressed, residual container volume, and orientation of the spray.FDA Drug Safety Communication: FDA continues to receive reports of a rare, but serious and potentially fatal adverse effect with the use of benzocaine sprays for medical procedures. Retrieved April 7, 2011.
Over-the-counter (OTC) oral drug products containing benzocaine should not be used for teething pain and are contraindicated in neonates, infants, and children younger than 2 years. Any potential benefits of using these products to treat teething pain do not outweigh their risks. Use of benzocaine can result in life-threatening and fatal methemoglobinemia. OTC benzocaine products should be used sparingly and only as needed in older children and adolescents; do not apply more frequently than 4 times per day. Signs and symptoms of methemoglobinemia may appear within minutes to 1 to 2 hours after benzocaine exposure and may occur with initial and/or subsequent use. Advise patients to seek immediate medical attention for discoloration (pale, gray, or blue-colored) of skin, lips, or nail beds; shortness of breath; fatigue; confusion; headache; lightheadedness; or rapid heart rate. Health care professionals using local anesthetics during medical procedures should monitor patients closely for methemoglobinemia, use co-oximetry when possible (methemoglobinemia can cause unreliable readings on standard two-wavelength pulse oximeters), and have resuscitation equipment and medications readily available, including methylene blue.Food and Drug Administration. FDA Drug Safety Communication: Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics. Several factors influence the amount of benzocaine contained in a single spray including manufacturer differences, varying concentrations, length of time actuator is depressed, residual container volume, and orientation of the spray.FDA Drug Safety Communication: FDA continues to receive reports of a rare, but serious and potentially fatal adverse effect with the use of benzocaine sprays for medical procedures. Retrieved April 7, 2011.
Lidocaine
Lidocaine application to oral mucosa can interfere with swallowing and increase the risk of aspiration. Patients should not ingest food for at least 1 hour after the use of anesthetic agents in the mouth or throat.
Local anesthetics, like lidocaine, should only be administered by a clinician trained in the diagnosis and management of drug-related toxicity and other acute emergencies that might arise from the administration of a regional anesthetic block. The immediate availability of oxygen, cardiopulmonary resuscitative equipment and drugs and the appropriate support personnel for the management of toxic reactions or emergencies must be ensured. Any delay in appropriate management may lead to the development of acidosis, cardiac arrest, and possibly death.
Lidocaine is contraindicated in patients with amide local anesthetic hypersensitivity. Parenteral preparations containing preservatives should not be used for spinal or epidural anesthesia. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products. There have been no reports of cross-sensitivity between lidocaine and either procainamide or quinidine.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.
Lidocaine does not provide adequate anesthesia in patients with collagen-vascular disease, such as Ehlers Danlos Type III. Lidocaine is relatively contraindicated in these conditions.Arendt-Nielsen L, Kaalund S, Bjerring P, et al. Insufficient effect of local analgesics in Ehlers Danlos type III patients (connective tissue disorder). Acta Anaesthesiol Scand 1990;34:358-61.
Methemoglobinemia has been reported with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), preexisting (congenital or idiopathic) methemoglobinemia, cardiac or pulmonary compromise (cardiac disease or pulmonary disease), those younger than 6 months, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing methemoglobinemia. Monitor such patients closely for signs and symptoms of methemoglobinemia if a local anesthetic must be used. Signs of methemoglobinemia may occur immediately or may be delayed hours after exposure. Immediately discontinue the local anesthetic to avoid serious central nervous system and cardiovascular adverse events, as methemoglobin concentrations may continue to rise. Patients may require supportive care such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.Kwok S, Fischer JL, Rogers JD. Benzocaine and lidocaine induced methemoglobinemia after bronchoscopy: a case report. J Med Case Reports 2008;2:16.Neuhaeuser C, Weigand N, Schaaf H, et al. Postoperative methemoglobinemia following infiltrative lidocaine administration for combined anesthesia in pediatric craniofacial surgery. Paediatr Anaesth 2008;18:125-31.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov.
Use lidocaine with caution in patients at increased risk of adverse events. Conditions that reduce hepatic blood flow such as hepatic disease and congestive heart failure may reduce hepatic metabolism and lead to drug accumulation, increasing the risk of developing systemic toxicity, particularly with parenteral, prescription topical jelly, or transdermal patch use.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.Lidocaine hydrochloride injection (intravenous for cardiac arrhythmias) package insert. Schaumburg, IL: American Pharmaceutical Partners, Inc.; 2002 Apr.Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system package insert. Las Vegas, NV: 7T Pharma LLC; 2018 Nov.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov.Xylocaine (lidocaine) 2% jelly package insert. Lake Forest, IL: Akorn, Inc.; 2018 Nov. Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated, particularly by those who are debilitated, pediatric patients, geriatric patients, or the acutely ill.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.Lidocaine hydrochloride injection (intravenous for cardiac arrhythmias) package insert. Schaumburg, IL: American Pharmaceutical Partners, Inc.; 2002 Apr.Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system package insert. Las Vegas, NV: 7T Pharma LLC; 2018 Nov.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov.Xylocaine (lidocaine) 2% jelly package insert. Lake Forest, IL: Akorn, Inc.; 2018 Nov. Excessive dosing by applying lidocaine transdermal patches to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to serious systemic adverse effects. Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 mcg/mL. The blood concentration of lidocaine is determined by the rate of systemic absorption and elimination. Longer duration of transdermal application, application of more than the recommended number of patches, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov.Lidocare (lidocaine 4%) patch package insert. Bristol, TN: NFI Consumer Products; 2015 Dec. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. The OBRA guidelines caution that antiarrhythmics can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals.Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.
Lidocaine is classified as FDA pregnancy category B. Reproductive studies conducted in rats have not demonstrated lidocaine-induced fetal harm; however, animal studies are not always predictive of human response. There are no adequate or well controlled studies of lidocaine in pregnant women.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb. Local anesthetics are known to cross the placenta rapidly and, when administered for epidural, paracervical, pudendal, or caudal block anesthesia, and to cause fetal toxicity. The frequency and extent of toxicity are dependent on the procedure performed. Maternal hypotension can result from regional anesthesia, and elevating the feet and positioning the patient on her left side may alleviate this effect. Topical ocular application of lidocaine is not expected to result in systemic exposure.Akten (lidocaine hcl) ophthalmic gel package insert. Lake Forest, IL: Akorn, Inc.; 2012 Dec. When lidocaine is used for dental anesthesia, no fetal harm has been observed; lidocaine is generally the dental anesthetic of choice during pregnancy and guidelines suggest the second trimester is the best time for dental procedures if they are necessary.Suresh L, Radfar L. Pregnancy and lactation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:672-682. Review. A study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.Michalowicz BS, DiAngelis AJ, Novak MJ, et al. Examining the safety of dental treatment in pregnant women. J Am Dent Assoc. 2008;139:685-695.
According to the manufacturers, caution should be exercised when lidocaine is administered to breastfeeding women (regardless of dosage formulation). Lidocaine is excreted in breast milk with a milk:plasma ratio of 0.4. Many specific dosage forms, including Lidoderm brand lidocaine transdermal patches, have not been studied in breastfeeding women.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov. The American Academy of Pediatrics lists lidocaine as usually compatible with breastfeeding.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789. When lidocaine is used for dental or short-term, limited local anesthesia, the healthy term infant can generally safely nurse as soon as the mother is awake and alert.Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breastfeeding mother. Am Fam Physician 2001; 64:119-126.] Suresh L, Radfar L. Pregnancy and lactation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:672-682. Review. Consider the benefits of breastfeeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternal drug exposure, healthcare providers are encouraged to report the adverse effect to the FDA.
Although specific forms of parenteral lidocaine are indicated for the treatment of some cardiac arrhythmias, it can worsen others. Intravenous (IV) lidocaine for the treatment of ventricular arrhythmias is contraindicated in patients with Adams-Stokes syndrome, Wolff-Parkinson-White syndrome, or with severe SA block, AV block, or intraventricular heart block. The administration of IV lidocaine for the elimination of ventricular ectopic beats to patients with bradycardia or incomplete heart block without prior acceleration of heart rate may cause a more serious ventricular arrhythmia or complete heart block. Lidocaine can increase the ventricular rate in patients with atrial fibrillation or atrial flutter. Use lidocaine with caution in patients with hypovolemia. Monitor blood pressure and the electrocardiogram during IV lidocaine administration. Promptly discontinue the infusion if signs of excessive depression of cardiac conductivity occur, such as prolongation of the PR interval, widening of the QRS interval, or appearance or aggravation of arrhythmias.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.Lidocaine hydrochloride injection in dextrose (intravenous for cardiac arrhythmias) package insert. Lake Forest, IL: Hospira, Inc.; 2014 Jan. Use both parenteral and topical formulations of lidocaine with caution in patients with severe shock (including cardiogenic shock and hemorrhagic shock) and heart block. Patients with impaired cardiac function, particularly AV block, may be less able to compensate for functional changes associated with prolonged AV conduction (i.e., PR or QT prolongation) caused by local anesthetics.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov.Xylocaine (lidocaine hydrochloride topical solution 4%) package insert. Schaumburg, IL: APP Pharmaceuticals; 2009 Mar.Xylocaine (lidocaine) 2% jelly package insert. Lake Forest, IL: Akorn, Inc.; 2018 Nov.Lidocaine injection package insert. Lake Forest, IL: Hospira, Inc.; 2008 Apr. Topical ocular application of lidocaine is not expected to result in systemic exposure.Akten (lidocaine hcl) ophthalmic gel package insert. Lake Forest, IL: Akorn, Inc.; 2012 Dec.
No lidocaine dosage adjustment needed in patients with renal impairment. However, the elimination of glycine xylidide (major active metabolite) is eliminated renally, and accumulation of the metabolite in severe renal failure (renal disease) theoretically could result in neurotoxicity.
Applying dermal, transdermal, or oromucosal lidocaine preparations to severely traumatized skin (e.g., mucosal or skin abrasion, eczema, burns), to large surface areas, or to warm skin (i.e., exercise, or application of thermal heat wraps or a heating pad immediately before or during topical lidocaine use) can increase its absorption, possibly increasing the risk of systemic toxicity. Also, applying large amounts of lidocaine or using an occlusive dressing (skin wraps) can increase absorption. Topical burn pads may be applied over burns and covered with tape or gauze while avoiding application of large quantities, particularly over raw surfaces or blistered areas.Alocane Emergency Burn Pads (lidocaine hydrochloride) package insert. Pleasant Prairie, WI: Quest Products, Inc.; 2020 Oct. Patches and administration via Zingo injection system should only be used on intact skin, and transoral delivery systems should only be applied to intact mucosa. Excessive dosing by applying patches to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine. Application of one additional Zingo at a new location is acceptable after a failed attempt at venous access. However, multiple administrations of Zingo at the same location are not recommended. Multiple Zingo applications could result in plasma concentrations that could produce systemic toxicity.Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system package insert. Las Vegas, NV: 7T Pharma LLC; 2018 Nov. At least 2 reports of deaths exist after application of topical anesthetics prior to cosmetic procedures. In both instances, women, aged 22 and 25 years, applied topical anesthetics to their legs and wrapped the treated area, as directed, in plastic wrap to enhance the numbing effect of the cream. Both women died from toxic effects of the topical anesthetic. The preparations used in both cases were compounded in pharmacies and contained high amounts of lidocaine and tetracaine. In order to reduce the risk of toxicity due to increased absorption of topical anesthetic, the FDA recommends patients use a topical anesthetic containing the lowest amount of medication needed to relieve pain, apply the medication sparingly, and only treat known or anticipated areas of pain. Further, do not apply the anesthetic to broken or irritated skin, be aware of potential adverse reactions, and do not cover or apply heat to the treated area.
Avoid unintended ocular exposure of lidocaine dermal, oromucosal, and transdermal products. Severe eye irritation has been reported in animals treated with similar products. If eye contact occurs, immediately wash the eye with water or saline and protect the eye until sensation returns. Lidocaine ophthalmic gel is intended for application to the eye surface; however, prolonged use may produce permanent corneal opacification and ulceration with accompanying visual loss.Akten (lidocaine hcl) ophthalmic gel package insert. Lake Forest, IL: Akorn, Inc.; 2012 Dec. Use with caution in patients with pre-existing cataracts or ocular trauma or ulceration.
To avoid accidental exposure and/or ingestion, advise patients and/or their caregivers to store and dispose of all lidocaine products out of the reach of any pediatric-age person and pets. It is important to note that whether new or used, lidocaine patches contain a large amount of lidocaine (at least 665 mg post-use). The potential exists for small kids or pets to suffer serious adverse reactions from unintended lidocaine exposure including chewing or ingesting a new or used lidocaine patch.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov.
When parenteral lidocaine is intended as a local anesthetic, avoid intravenous administration, intraarterial administration, or intrathecal administration. Unintended intravenous or intraarterial administration may result in cardiac arrest and may require prolonged resuscitation. Further, do not administer preservative-containing parenteral lidocaine via intrathecal routes. To avoid intravascular administration of lidocaine during local anesthetic procedures, aspiration should be performed before the local anesthetic is injected and after repositioning of the needle. During epidural administration, a test dose should be administered initially and the patient should be monitored for CNS and cardiovascular toxicity, as well as signs of inadvertent intrathecal administration (see Adverse Reactions). Syringe aspiration should also be performed before and during each supplemental injection in continuous catheter techniques. Clinicians should be aware that the absence of blood return does not guarantee that intravascular injection has been avoided.
Patients receiving local head and neck anesthesia including retrobulbar, stellate ganglion, and dental blocks, are at increased risk of CNS toxicity similar to the systemic toxicity seen with unintentional intravascular injections of large doses of lidocaine. These reactions may be due to potential intraarterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Patients receiving these blocks should have their ventilatory and circulatory systems monitored closely. Recommended doses should not be exceeded in these patients.
When local anesthetics, like lidocaine, are used for retrobulbar block during ocular surgery, lack of corneal sensation should not be relied upon to determine whether or not the patient is ready for surgery. Lack of corneal sensation usually precedes clinically acceptable external ocular muscle akinesia.
Parenteral use of lidocaine requires an experienced clinician and requires a specialized care setting. Lidocaine preparations containing preservatives should not be used for epidural or spinal anesthesia. Patients with the following conditions should receive spinal anesthesia with caution: pre-existing CNS disorders such as poliomyelitis, pernicious anemia, paralysis from nerve injuries or syphilis; pediatric patients younger than 16 years, or elderly patients; chronic backache; preoperative headache; hypotension; hypertension; arthritis or spinal deformity; technical problems (persistent paresthesias, persistent bloody tap); psychotic or uncooperative patients. Consult standard textbooks for specific techniques and precautions for spinal anesthetic procedures. Epidural, local, nerve block and spinal administration of lidocaine are contraindicated in patients with the following: infection or inflammation at the injection site, bacteremia (sepsis), platelet abnormalities, thrombocytopenia less than 100,000/mm3, increased bleeding time, uncontrolled coagulopathy or bleeding, or anticoagulant therapy. Lumbar and caudal epidural anesthesia should be used with extreme caution in patients with existing neurological disease, spinal deformities, sepsis, and severe hypertension. Use caution when applying topical lidocaine to mucous membranes in the presence of sepsis due to the potential for rapid systemic absorption.Xylocaine (lidocaine hydrochloride topical solution 4%) package insert. Schaumburg, IL: APP Pharmaceuticals; 2009 Mar.Xylocaine (lidocaine) 2% jelly package insert. Lake Forest, IL: Akorn, Inc.; 2018 Nov. Patients with platelet disorders or those with bleeding tendencies may be at risk for superficial dermal bleeding when lidocaine is administered intradermally for topical anesthesia.Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system package insert. Las Vegas, NV: 7T Pharma LLC; 2018 Nov.
During labor and obstetric delivery, local anesthetics, like lidocaine, can cause varying degrees of maternal, fetal, and neonatal toxicities. The potential for toxicity is related to the procedure performed, the type and amount of drug used, and the technique of administration. Appropriate patient positioning during obstetric delivery may decrease maternal hypotension that can result from regional anesthesia. Injection of the local anesthetic should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Epidural, spinal, paracervical, or pudendal nerve block may alter the forces of parturition. The use of obstetrical anesthesia may alter the duration of various phases of labor and increase the need for forceps assistance. Electronic fetal monitoring for signs of fetal distress is highly recommended.
Lidocaine is not approved for continuous intraarticular infusion administration. Infusion of local anesthetics into a joint space may have caused chondrolysis. Local anesthetics are not indicated for continuous intraarticular postoperative infusions or for use with infusion devices such as elastomeric pumps.
Physicians should weigh the possible risks versus benefits when considering obstetrical paracervical nerve block with parenteral lidocaine in situations of fetal prematurity, toxemia of pregnancy, and fetal distress. Adherence to the recommended dosage is critical during obstetrical paracervical block. Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection. Use of paracervical block in early pregnancy (i.e., anesthesia for elective abortion) may result in rapid systemic absorption and can result in maternal seizures or cardiovascular collapse. The recommended dose of the local anesthetic should not be exceeded. Injections should be administered slowly with frequent aspirations. Allow a 5-minute interval between administration to each side.
Use lidocaine with caution in patients with a genetic predisposition to malignant hyperthermia. Although it is unknown whether lidocaine triggers this reaction, it is recommended that a standard protocol for management be available when lidocaine is administered in hospital environments.Lidocaine injection package insert. Lake Forest, IL: Hospira, Inc.; 2008 Apr.
Lidocaine dosages in pediatric patients should be reduced, commensurate with age, body weight and physical condition. When multiple formulations of lidocaine are used at once, the amount systemically absorbed from all formulations must be considered. Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated by pediatric patients, particularly by those who are debilitated or the acutely ill.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.Lidocaine hydrochloride injection (intravenous for cardiac arrhythmias) package insert. Schaumburg, IL: American Pharmaceutical Partners, Inc.; 2002 Apr.Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system package insert. Las Vegas, NV: 7T Pharma LLC; 2018 Nov.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov.Xylocaine (lidocaine) 2% jelly package insert. Lake Forest, IL: Akorn, Inc.; 2018 Nov. Similar increases in systemic exposure are possible with repeat topical application. Certain products, such as lidocaine transdermal patches, have not been FDA-approved for application to pediatric patients.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov. Non-prescription (OTC) products should not be used without healthcare professional advice in those under 2 years of age, or as directed on the product label. Do not use lidocaine viscous solution for the treatment of teething pain in infants and young children due to the risk of serious adverse reactions, including seizures, cardiopulmonary arrest, severe brain injury, and death. FDA Drug Safety Communication: FDA recommends not using lidocaine to treat teething pain and requires new Boxed Warning. Retrieved June 26, 2014. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm402240.htm The FDA reviewed 22 cases of serious adverse events that occurred in infants and young children between 5 months and 3.5 years of age after receiving lidocaine viscous solution for the treatment of mouth pain due to teething or stomatitis or who had accidental ingestions. Of the 22 cases, 6 cases resulted in death, 3 were categorized as life-threatening, 11 required hospitalization, and 2 required medical intervention without hospitalization. The FDA recommends against the use of topical pain relievers for teething pain due to the fact that they wash out of the mouth within minutes of application and can cause serious adverse reactions if they are swallowed in excessive amounts. FDA Drug Safety Communication: FDA recommends not using lidocaine to treat teething pain and requires new Boxed Warning. Retrieved June 26, 2014. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm402240.htm Advise parents and caregivers with teething pain concerns to follow the American Academy of Pediatrics recommendations for the management of teething pain, which include using a teething ring chilled in the refrigerator (not frozen) and gently rubbing or massaging the gums with a finger. FDA Drug Safety Communication: FDA recommends not using lidocaine to treat teething pain and requires new Boxed Warning. Retrieved June 26, 2014. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm402240.htm For other conditions, the use of viscous lidocaine in neonates, infants, and children 3 years of age and younger should be limited to those situations where safer alternatives are not available or have failed. To ensure safety, doses should be measured by an accurate device, administered no more often than every 3 hours, used only for the prescribed indication, and stored safely out of the reach of children immediately after use.Lidocaine Hydrochloride Oral Topical Solution (Viscous) 2% package insert. Lake Zurich, IL: Fresenius Kabi, Inc.; 2014 Sep. When topical anesthetics are used in the mouth, the topical anesthesia may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested for 60 minutes following use of local anesthetic preparations in the mouth or throat area. This is particularly important in children because of their frequency of eating.Xylocaine (lidocaine hydrochloride topical solution 4%) package insert. Schaumburg, IL: APP Pharmaceuticals; 2009 Mar.
Phenylephrine HCl
Phenylephrine, particularly when administered intravenously, should be avoided in patients with severe organic cardiac disease including coronary artery disease (e.g., angina, history of myocardial infarction, acute myocardial infarction) and dilated cardiomyopathy. Phenylephrine injection is contraindicated in patients with severe hypertension and/or ventricular tachycardia. This may include patients with arrhythmias associated with tachycardia (atrial fibrillation, atrial flutter, ventricular fibrillation) because of its detrimental cardiovascular effects in these conditions (i.e., increased myocardial oxygen demand, chronotropy, proarrhythmic potential, and vasoactivity). Phenylephrine injection should be used with caution in patients with bradycardia or AV block. All forms of phenylephrine should be used with caution in patients with uncontrolled hypertension due to the increased likelihood of adverse cardiac events. Phenylephrine can cause a decrease in cardiac output, and extreme caution should be used when administering the drug, parenterally or orally, to patients with arteriosclerosis, to elderly patients, or to patients with coronary artery disease or heart failure.
Phenylephrine should be avoided in patients with cerebrovascular disease such as cerebral arteriosclerosis, aneurysm, intracranial bleeding, history or stroke or organic brain syndrome because of the potential sympathomimetic (presumably alpha) effects in the CNS and the potential for cerebrovascular hemorrhage, especially with intravenous use.
Phenylephrine should be avoided in patients with sulfite hypersensitivity unless the patient is being treated for an emergent condition such as anaphylaxis or cardiac arrest. Phenylephrine formulations contain sodium metabisulfite, a sulfite that can cause severe allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes in susceptible patients. The overall presence of sulfite hypersensitivity in the general population is unknown but presumed to be low. Sulfite hypersensitivity is seen most often in asthmatic patients compared to non-asthmatic patient.Phenylephrine hydrochloride injection package insert. Lake Forest, IL: Hospira, Inc.; 2005 Nov.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun.
Systemic phenylephrine products should be used with caution in men with symptomatic, benign prostatic hypertrophy, due to the potential for urinary retention.
Use phenylephrine with caution in patients with extensive peripheral vascular disease. Phenylephrine can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun.
Monitor renal function closely in patients with septic shock. If used for septic shock, phenylephrine can increase the need for renal replacement therapy.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun.
Use caution when administering phenylephrine to patients with hepatic disease. Dose-response data indicate decreased responsiveness to phenylephrine in patients with liver cirrhosis. Larger doses may be needed in patients with hepatic disease.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun.
Use caution when administering phenylephrine to patients with end stage renal disease. Dose-response data indicate increased responsiveness to phenylephrine in these patients. Lower doses may be needed in patients with renal failure.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun.
Use phenylephrine with caution in patients with autonomic neuropathy. Patients with autonomic dysfunction, such as those with spinal cord injury, may have an increased blood pressure response to adrenergic drugs.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun.
Prilocaine
Local anesthetics like prilocaine should only be administered by a clinician trained in the diagnosis and management of drug-related toxicity and other acute emergencies that might arise from the administration of a regional anesthetic block. The immediate availability of oxygen, cardiopulmonary resuscitative equipment, and drugs and the appropriate support personnel for the management of toxic reactions or emergencies must be ensured. Any delay in appropriate management may lead to the development of acidosis, cardiac arrest, and possibly death.
Prilocaine is contraindicated for use in patients with known amide local anesthetic hypersensitivity.
Intravenous administration or intraarterial administration of prilocaine should be avoided. Unintended intravenous or intraarterial administration may result in cardiac arrest and may require prolonged resuscitation. To avoid intravascular administration of prilocaine during local anesthetic procedures, aspiration should be performed before the local anesthetic is injected and after repositioning of the needle. Clinicians should be aware that the absence of blood return does not guarantee that intravascular injection has been avoided.
Patients receiving local head and neck anesthesia, including dental blocks, are at increased risk of CNS toxicity similar to systemic toxicity seen with unintentional intravascular injections of large doses. These reactions may be due to potential intraarterial injection of the local anesthetic like prilocaine with retrograde flow to the cerebral circulation. Patients receiving these blocks should have their ventilatory and circulatory systems monitored closely. Recommended doses should not be exceeded in these patients.
Nerve block injections of prilocaine are contraindicated in patients with infection or inflammation at the injection site, bacteremia, platelet abnormalities, thrombocytopenia (platelet count less than 100,000/mm3), increased bleeding time, uncontrolled coagulopathy, or anticoagulant therapy.
Local anesthetics such as prilocaine should be used with caution in patients with hypotension, hypovolemia or dehydration, myasthenia gravis, shock, or cardiac disease. Patients with impaired cardiac function, particularly AV block, may be less able to compensate for functional changes associated with prolonged A-V conduction (i.e., PR or QT prolongation) caused by local anesthetics.
Prilocaine is contraindicated in patients with congenital or idiopathic methemoglobinemia. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), preexisting (congenital or idiopathic) methemoglobinemia, cardiac or pulmonary compromise (cardiac disease or pulmonary disease), neonates and infants younger than 6 months, and those with concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing methemoglobinemia. Monitor such patients closely for signs and symptoms of methemoglobinemia if a local anesthetic must be used. Signs of methemoglobinemia may occur immediately or may be delayed hours after exposure. Immediately discontinue the local anesthetic to avoid serious central nervous system and cardiovascular adverse events, as methemoglobin concentrations may continue to rise. Patients may require supportive care such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov.
Geriatric patients, especially those receiving treatment for hypertension, may be at increased risk for the hypotensive effects of prilocaine.
Due to extensive liver metabolism of prilocaine, dosage adjustments may be needed in patients with hepatic disease. Patients with hepatic disease may be more susceptible to the potential toxicities of prilocaine. Dosage adjustments or extension of the dosing interval may be required.
Prilocaine is classified as FDA pregnancy risk category B. Teratogenicity has not been observed in animal studies.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov. Placental transfer of local anesthetics, such as prilocaine, is dependent upon the degree of plasma protein binding, ionization, and lipid solubility of each agent. Fetal to maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding since only free, unbound drug is available for placental transfer. There are no adequate safety data on the use of prilocaine as a dental anesthetic in pregnant women. Use of other local anesthetics during obstetric delivery can cause maternal, fetal, or neonatal toxicity which is dependent upon the procedure performed, the type and amount of drug used, and drug administration technique.Bupivacaine injection and bupivacaine; epinephrine injection package insert. Lake Forest, IL: Hospira, Inc.; 2018 Nov. Because the fetal risk after maternal exposure to prilocaine in dental procedures is unknown and because animal reproduction studies are not always predictive of human response, prilocaine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov. However, a study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.Michalowicz BS, DiAngelis AJ, Novak MJ, et al. Examining the safety of dental treatment in pregnant women. J Am Dent Assoc. 2008;139:685-695. Additionally, most dental guidelines suggest that the second trimester is the best time for dental procedures if they are necessary; lidocaine (FDA pregnancy category B) is a preferred agent for use.Suresh L, Radfar L. Pregnancy and lactation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:672-682. Review. The effects of prilocaine in labor and delivery are unknown.
According to the manufacturer, it is not known if prilocaine is excreted in breast milk, and caution is advisable if administering prilocaine to a breastfeeding mother.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov. Local anesthetics such as lidocaine and bupivacaine are minimally excreted into breast milk; however, the potential for adverse effects in the nursing infant is low due to poor oral absorption.Ortega D, Viviand X, Lorec AM, et al. Excretion of lidocaine and bupivacaine in breast milk following epidural anesthesia for cesarean delivery. Acta Anaesthesiol Scand 1999;43:394-397.Zeisler JA, Gaarder TD, De Mesquita SA. Lidocaine excretion in breast milk. Drug Intell Clin Pharm 1986;20:691-3.Chang ZM, Heaman MI. Epidural analgesia during labor and delivery: effects on the initiation and continuation of effective breastfeeding. J Hum Lact 2005;21:305-314. Gastrointestinal absorption of prilocaine after oral ingestion by a nursing infant is also expected to be low. Prilocaine has not been evaluated by the American Academy of Pediatrics (AAP); however, the AAP considers lidocaine to be usually compatible with breastfeeding.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789. In general, there are no contraindications to using any of the local anesthetics for dentistry purposes in the lactating mother, and lidocaine is often a preferred agent during pregnancy and lactation.Suresh L, Radfar L. Pregnancy and lactation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:672-682. Review. The healthy term infant can safely nurse as soon after dental procedures, like other surgeries, as the mother is awake and alert.Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breastfeeding mother. Am Fam Physician 2001; 64:119-126. Consider the benefits of breastfeeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternal drug exposure, healthcare providers are encouraged to report the adverse effect to the FDA.
Tetracaine
Local anesthetics like tetracaine should only be administered by a clinician trained in the diagnosis and management of drug-related toxicity and other acute emergencies that might arise from the administration of a regional anesthetic block. The immediate availability of oxygen, cardiopulmonary resuscitative equipment and drugs and the appropriate support personnel for the management of toxic reactions or emergencies must be ensured. Any delay in appropriate management may lead to the development of acidosis, cardiac arrest, and possibly death.
Tetracaine is contraindicated in patients with ester local anesthetic hypersensitivity or para-aminobenzoic acid, PABA hypersensitivity. Some formulations contain acetone sodium bisulfite and may be inappropriate for use by patients with sulfite hypersensitivity.
Local anesthetics like tetracaine should be used with caution in patients with hypotension, hypovolemia or dehydration, myasthenia gravis, shock, or cardiac disease. Patients with impaired cardiac function, particularly AV block, may be less able to compensate for functional changes associated with prolonged A-V conduction (i.e., PR or QT prolongation) caused by local anesthetics.
Intravenous administration or intraarterial administration of tetracaine should be avoided. Unintended intravenous or intraarterial administration may result in cardiac arrest and may require prolonged resuscitation. To avoid intravascular administration of procaine during local anesthetic procedures, aspiration should be performed before the local anesthetic is injected and after repositioning of the needle. Syringe aspiration should also be performed before and during each supplemental injection in continuous catheter techniques. Clinicians should be aware that the absence of blood return does not guarantee that intravascular injection has been avoided.
Spinal and nerve block injections of tetracaine are contraindicated in patients with the following: infection or inflammation at the injection site, bacteremia, platelet abnormalities, thrombocytopenia < 100,000/mm3, increased bleeding time, uncontrolled coagulopathy, or anticoagulant therapy.
Patients with the following conditions should receive spinal anesthesia with caution: pre-existing CNS disorders such as poliomyelitis, pernicious anemia, paralysis from nerve injuries or syphilis; infants, children < 16 years, or geriatric patients; chronic backache; preoperative headache; hypotension; hypertension; arthritis or spinal deformity; technical problems (persistent paresthesias, persistent bloody tap); psychotic or uncooperative patients. Consult standard textbooks for specific techniques and precautions for spinal anesthetic procedures. Elderly patients, especially those receiving treatment for hypertension, may be at increased risk for the hypotensive effects of local anesthetics like tetracaine.
Prolonged use of topical anesthetics is not recommended. Applying topical tetracaine preparations to severely traumatized skin (e.g., skin abrasion, eczema, burns), to large surface areas, or to warm skin (i.e., after exercise, applying thermal heat wraps or heating pads) can increase its absorption, possibly increasing the risk of systemic toxicity. Also, applying large amounts of tetracaine or using an occlusive dressing (skin wraps) can increase tetracaine absorption. At least 2 reports of deaths exist after application of topical anesthetics prior to cosmetic procedures. In both instances, women, aged 22 and 25 years, applied topical anesthetics to their legs and wrapped the treated area, as directed, in plastic wrap to enhance the numbing effect of the cream. Both women died from toxic effects of the topical anesthetic. The preparations used in both cases were compounded in pharmacies and contained high amounts of lidocaine and tetracaine. In order to reduce the risk of toxicity due to increased absorption of topical anesthetic, the FDA recommends patients use a topical anesthetic containing the lowest amount of medication needed to relieve pain and apply the medication sparingly and only treat known or anticipated areas of pain. Further, do not apply the anesthetic to broken or irritated skin, be aware of potential adverse reactions, and do not cover or apply heat to the treated area.
Ester-type local anesthetics like tetracaine should be used cautiously, if at all, in patients with low plasma levels of pseudocholinesterase (e.g., pseudocholinesterase deficiency).
Administer tetracaine to a pregnant woman only if clearly needed and if the potential benefits outweigh the risk; it is not known whether tetracaine can cause fetal harm when administered to a pregnant woman or if can impair fertility. No adequate or well-controlled studies have been conducted to evaluate the use of tetracaine during human pregnancy, and there are no animal developmental or reproductive toxicity studies. While tetracaine injection has recognized utility during labor and obstetric delivery, the effect of the drug on labor duration, forceps delivery incidence, newborn status, and later growth and development of the child are unknown.Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun. The amount of tetracaine reaching the systemic formulation after topical or ophthalmic administration is unknown but is probably low.Briggs GG, Freeman RK, Yaffee SJ. Tetracaine. In: Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 9th ed. Philadelphia: Lippincott Williams & Wilkins: 2011;1412-13. Tetracaine hydrochloride ophthalmic solution. Tampa, FL: Bausch and Lomb; 2022 Feb.
It is not known if tetracaine is distributed into human milk. Tetracaine is rapidly metabolized following absorption into the plasma.Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun. There are no data available to describe the effects of tetracaine ophthalmic administration on milk production/excretion.Tetracaine hydrochloride ophthalmic solution. Tampa, FL: Bausch and Lomb; 2022 Feb. Use caution when tetracaine is given to a breastfeeding woman. Consider the mother’s clinical need for tetracaine and any potential adverse effects on the breastfed infant from tetracaine or the underlying maternal condition.Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun. Tetracaine hydrochloride ophthalmic solution. Tampa, FL: Bausch and Lomb; 2022 Feb. Systemic absorption after topical administration is expected to be minimal and is unlikely to affect a breastfed infant; however, it is recommended that topical formulations of tetracaine be applied away from the breast.National Institutes of Health (NIH). Tetracaine monograph. LactMed: Drug and Lactation Database. Available at http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~hiRQ6t:1. Accessed March 28th, 2012.
Tetracaine ophthalmic solution is NOT intended for patient self-administration, and must be administered under the direct supervision of a health care provider. After ocular use, the eye may be inadvertently damaged while anesthetic effects remain. Patients should avoid touching, rubbing, or wiping the eyes for at least 10 to 20 minutes. Contact lenses should not be inserted until the anesthetic effects of tetracaine have completely waned (about 20 minutes). Prolonged use may result in corneal epithelial toxicity, which may progress to permanent corneal damage.Tetracaine hydrochloride ophthalmic solution. Tampa, FL: Bausch and Lomb; 2022 Feb.
Lidocaine
Lidocaine is classified as FDA pregnancy category B. Reproductive studies conducted in rats have not demonstrated lidocaine-induced fetal harm; however, animal studies are not always predictive of human response. There are no adequate or well controlled studies of lidocaine in pregnant women.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb. Local anesthetics are known to cross the placenta rapidly and, when administered for epidural, paracervical, pudendal, or caudal block anesthesia, and to cause fetal toxicity. The frequency and extent of toxicity are dependent on the procedure performed. Maternal hypotension can result from regional anesthesia, and elevating the feet and positioning the patient on her left side may alleviate this effect. Topical ocular application of lidocaine is not expected to result in systemic exposure.Akten (lidocaine hcl) ophthalmic gel package insert. Lake Forest, IL: Akorn, Inc.; 2012 Dec. When lidocaine is used for dental anesthesia, no fetal harm has been observed; lidocaine is generally the dental anesthetic of choice during pregnancy and guidelines suggest the second trimester is the best time for dental procedures if they are necessary.Suresh L, Radfar L. Pregnancy and lactation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:672-682. Review. A study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.Michalowicz BS, DiAngelis AJ, Novak MJ, et al. Examining the safety of dental treatment in pregnant women. J Am Dent Assoc. 2008;139:685-695.
Phenylephrine HCl
Phenylephrine is classified as FDA pregnancy category C.Phenylephrine hydrochloride package insert. Eatontown, NJ: West-ward Pharmaceuticals; 2011 May. It should be used during pregnancy with caution. Topically applied phenylephrine is expected to provide reduced exposure systemically versus oral or injectable routes. Systemic phenylephrine must be used only when the benefit to the mother outweighs the risk to the fetus during late pregnancy, labor, or obstetric delivery; when used during this time it can cause fetal anoxia and/or bradycardia due to increased uterine contractility or decreased uterine blood flow.Smith NT, Corbascio AN. The use and misuse of pressor agents. Anesthesiology 1970;33:58-101. Obstetricians should also be aware of the risk of severe persistent hypertension if it is used during labor and delivery and the possibility of rupture of a cerebral blood vessel in the postpartum period.Phenylephrine hydrochloride package insert. Eatontown, NJ: West-ward Pharmaceuticals; 2011 May.
Prilocaine
Prilocaine is classified as FDA pregnancy risk category B. Teratogenicity has not been observed in animal studies.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov. Placental transfer of local anesthetics, such as prilocaine, is dependent upon the degree of plasma protein binding, ionization, and lipid solubility of each agent. Fetal to maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding since only free, unbound drug is available for placental transfer. There are no adequate safety data on the use of prilocaine as a dental anesthetic in pregnant women. Use of other local anesthetics during obstetric delivery can cause maternal, fetal, or neonatal toxicity which is dependent upon the procedure performed, the type and amount of drug used, and drug administration technique.Bupivacaine injection and bupivacaine; epinephrine injection package insert. Lake Forest, IL: Hospira, Inc.; 2018 Nov. Because the fetal risk after maternal exposure to prilocaine in dental procedures is unknown and because animal reproduction studies are not always predictive of human response, prilocaine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov. However, a study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.Michalowicz BS, DiAngelis AJ, Novak MJ, et al. Examining the safety of dental treatment in pregnant women. J Am Dent Assoc. 2008;139:685-695. Additionally, most dental guidelines suggest that the second trimester is the best time for dental procedures if they are necessary; lidocaine (FDA pregnancy category B) is a preferred agent for use.Suresh L, Radfar L. Pregnancy and lactation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:672-682. Review. The effects of prilocaine in labor and delivery are unknown.
Tetracaine
Administer tetracaine to a pregnant woman only if clearly needed and if the potential benefits outweigh the risk; it is not known whether tetracaine can cause fetal harm when administered to a pregnant woman or if can impair fertility. No adequate or well-controlled studies have been conducted to evaluate the use of tetracaine during human pregnancy, and there are no animal developmental or reproductive toxicity studies. While tetracaine injection has recognized utility during labor and obstetric delivery, the effect of the drug on labor duration, forceps delivery incidence, newborn status, and later growth and development of the child are unknown.Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun. The amount of tetracaine reaching the systemic formulation after topical or ophthalmic administration is unknown but is probably low.Briggs GG, Freeman RK, Yaffee SJ. Tetracaine. In: Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 9th ed. Philadelphia: Lippincott Williams & Wilkins: 2011;1412-13.Tetracaine hydrochloride ophthalmic solution. Tampa, FL: Bausch and Lomb; 2022 Feb.
Benzocaine
It is not known whether benzocaine is excreted in human breast milk, however in general, topically applied benzocaine is unlikely to affect the nursing infant if it is applied away from the breast. Benzocaine has been associated with life-threatening cases of methemoglobin; products should be applied and used only as directed and the drug should never be applied to the breast or nipple in order to avoid infant ingestion.FDA Drug Safety Communication: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth. Retrieved April 7, 2011. Benzocaine was not evaluated by previous American Academy of Pediatrics (AAP) recommendations; however, the recommendations considered lidocaine as usually compatible with breastfeeding.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.
Lidocaine
According to the manufacturers, caution should be exercised when lidocaine is administered to breastfeeding women (regardless of dosage formulation). Lidocaine is excreted in breast milk with a milk:plasma ratio of 0.4. Many specific dosage forms, including Lidoderm brand lidocaine transdermal patches, have not been studied in breastfeeding women.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov. The American Academy of Pediatrics lists lidocaine as usually compatible with breastfeeding.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789. When lidocaine is used for dental or short-term, limited local anesthesia, the healthy term infant can generally safely nurse as soon as the mother is awake and alert.Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breastfeeding mother. Am Fam Physician 2001; 64:119-126.] Suresh L, Radfar L. Pregnancy and lactation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:672-682. Review. Consider the benefits of breastfeeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternal drug exposure, healthcare providers are encouraged to report the adverse effect to the FDA.
Phenylephrine HCl
It is not known whether phenylephrine is distributed into breast milk; however, the low molecular weight of the drug would suggest possible passage. According to the manufacturer, caution should be exercised when administering it to women who are breastfeeding their infants.Phenylephrine hydrochloride package insert. Eatontown, NJ: West-ward Pharmaceuticals; 2011 May. However, since phenylephrine is generally poorly absorbed, the potential overall absorption by an infant following breastfeeding may be minimal. In the treatment of nasal congestion, non-systemic decongestant preparations such as intranasal sodium chloride or temporary use of intranasal decongestants should be considered prior to consideration of an oral decongestant. Consider the benefits of breastfeeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Prilocaine
According to the manufacturer, it is not known if prilocaine is excreted in breast milk, and caution is advisable if administering prilocaine to a breastfeeding mother.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov. Local anesthetics such as lidocaine and bupivacaine are minimally excreted into breast milk; however, the potential for adverse effects in the nursing infant is low due to poor oral absorption.Ortega D, Viviand X, Lorec AM, et al. Excretion of lidocaine and bupivacaine in breast milk following epidural anesthesia for cesarean delivery. Acta Anaesthesiol Scand 1999;43:394-397.Zeisler JA, Gaarder TD, De Mesquita SA. Lidocaine excretion in breast milk. Drug Intell Clin Pharm 1986;20:691-3.Chang ZM, Heaman MI. Epidural analgesia during labor and delivery: effects on the initiation and continuation of effective breastfeeding. J Hum Lact 2005;21:305-314. Gastrointestinal absorption of prilocaine after oral ingestion by a nursing infant is also expected to be low. Prilocaine has not been evaluated by the American Academy of Pediatrics (AAP); however, the AAP considers lidocaine to be usually compatible with breastfeeding.American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789. In general, there are no contraindications to using any of the local anesthetics for dentistry purposes in the lactating mother, and lidocaine is often a preferred agent during pregnancy and lactation.Suresh L, Radfar L. Pregnancy and lactation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:672-682. Review. The healthy term infant can safely nurse as soon after dental procedures, like other surgeries, as the mother is awake and alert.Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breastfeeding mother. Am Fam Physician 2001; 64:119-126. Consider the benefits of breastfeeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternal drug exposure, healthcare providers are encouraged to report the adverse effect to the FDA.
Tetracaine
It is not known if tetracaine is distributed into human milk. Tetracaine is rapidly metabolized following absorption into the plasma.Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun. There are no data available to describe the effects of tetracaine ophthalmic administration on milk production/excretion.Tetracaine hydrochloride ophthalmic solution. Tampa, FL: Bausch and Lomb; 2022 Feb. Use caution when tetracaine is given to a breastfeeding woman. Consider the mother’s clinical need for tetracaine and any potential adverse effects on the breastfed infant from tetracaine or the underlying maternal condition.Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun. Tetracaine hydrochloride ophthalmic solution. Tampa, FL: Bausch and Lomb; 2022 Feb. Systemic absorption after topical administration is expected to be minimal and is unlikely to affect a breastfed infant; however, it is recommended that topical formulations of tetracaine be applied away from the breast.National Institutes of Health (NIH). Tetracaine monograph. LactMed: Drug and Lactation Database. Available at http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~hiRQ6t:1. Accessed March 28th, 2012.
Benzocaine
Contact dermatitis from benzocaine use can result in pruritus, erythema, edema, pain, rash (unspecified), and urticaria. Angioedema occurs with less frequency, although it requires prompt medical attention. Photosensitivity has rarely been reported in patients receiving topical benzocaine.
Benzocaine, like all local anesthetics, can produce significant CNS and cardiovascular toxicity when high serum concentrations are achieved. This rarely occurs, however, because benzocaine is poorly absorbed. CNS toxicity usually presents with symptoms of CNS stimulation such as anxiety, apprehension, restlessness, nervousness, disorientation, confusion, dizziness, headache, blurred vision, tremor, shivering, and/or seizures. Subsequently, depressive symptoms can occur including drowsiness, coma, and respiratory arrest. In some patients, the symptoms of CNS toxicity can be minor and transient. Adverse cardiovascular effects include myocardial depression; sinus bradycardia, sinus tachycardia, or other cardiac arrhythmias; hypotension or hypertension; cardiovascular collapse; and/or cardiac arrest. These effects typically occur with high plasma drug concentrations but have occurred with smaller doses in rare cases. Severe adverse effects from benzocaine administration should be treated with general supportive physiologic measures such as oxygen therapy, assisted ventilation, and IV fluids. Seizures can be treated with a slow infusion of IV diazepam, although this should be done cautiously because diazepam is also a CNS depressant.
Use of benzocaine can result in methemoglobinemia, which is a rare but serious condition where too much of the hemoglobin in red blood cells becomes unable to bind and carry oxygen. Severe cases of methemoglobinemia can result in death. Signs and symptoms of methemoglobinemia may appear within minutes to 1 to 2 hours after benzocaine exposure and may occur with initial and/or subsequent use. Advise patients to seek immediate medical attention for discoloration (pale, gray, or blue-colored) of skin, lips, or nail beds; shortness of breath; fatigue; confusion; headache; lightheadedness; or rapid heart rate. Chocolate-brown rather than red blood is characteristic and may indicate methemoglobinemia, but this change is a late sign. Health care professionals using local anesthetics during medical procedures should monitor patients closely for methemoglobinemia, use co-oximetry when possible, and have resuscitation equipment and medications readily available, including methylene blue. Use benzocaine products in the smallest amount possible in order to relieve pain. Over-the-counter (OTC) drug products containing benzocaine should not be used to treat infants and children younger than 2 years. More than 400 cases of benzocaine-associated methemoglobinemia have been reported to the FDA or published in the medical literature since 1971. Of the 119 cases recently evaluated, most were serious and required treatment. Twenty-two cases (18%) occurred in pediatric patients; 11 of these were in patients younger than 2 years. Four of the 119 cases (3%) resulted in death, including 1 infant and 3 adults. Thirty-six cases (30%) had a reported methemoglobinemia concentration of 30% to 55% (normal concentration is 1% to 2%). Seventeen cases (14%) had a reported methemoglobinemia concentration of 55% or more, which is considered life-threatening.Food and Drug Administration. FDA Drug Safety Communication: Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics.
Lidocaine
Lidocaine crosses the blood brain barrier and can produce significant central nervous system (CNS) toxicity, particularly when high plasma concentrations (more than 6 mcg/mL free base) are achieved. CNS manifestations are excitatory and/or depressant and may be characterized by lightheadedness (dizziness), anxiety (i.e., nervousness or apprehension), restlessness, euphoria, confusion, drowsiness, tinnitus, blurred vision or double vision, vomiting, metallic taste, dysgeusia, sensations of heat (hot flashes), cold or numbness, hyperesthesia, hypoesthesia, asthenia, twitching, tremor, convulsions (seizures), unconsciousness, respiratory depression, and respiratory arrest. Agitation, dysarthria, oral hypoesthesia, and disorientation have also been reported with systemic use. The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest. Drowsiness after the administration of lidocaine is usually an early sign of a high blood concentration of the drug and may occur as a consequence of rapid absorption. In some patients, the symptoms of CNS toxicity are minor and transient.Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov.Xylocaine (lidocaine hydrochloride topical solution 4%) package insert. Schaumburg, IL: APP Pharmaceuticals; 2009 Mar.Lidocaine Hydrochloride Oral Topical Solution (Viscous) 2% package insert. Lake Zurich, IL: Fresenius Kabi, Inc.; 2014 Sep.Lidocaine Ointment 5% package insert. Melville, NY: E. Fougera & Co.; 2007 Sept.Xylocaine (lidocaine) 2% jelly package insert. Lake Forest, IL: Akorn, Inc.; 2018 Nov.Lidocaine injection package insert. Lake Forest, IL: Hospira, Inc.; 2008 Apr.ZTlido (lidocaine topical system) package insert. San Diego, CA: Scilex Pharmaceuticals, Inc.; 2021 Apr. Dizziness and vomiting occurred in 0.9% and 1% of patients, respectively, who were treated with the lidocaine intradermal injection system during clinical trials.Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system package insert. Las Vegas, NV: 7T Pharma LLC; 2018 Nov.
During caudal or lumbar epidural block, unintentional penetration of the subarachnoid space may occur. Adverse effects depend upon the amount of drug given subdurally and may include spinal block of varying magnitude, low blood pressure secondary to spinal block, fecal incontinence and urinary incontinence, and loss of perineal sensation and sexual function. In a prospective review of 10,440 patients who received lidocaine HCl for spinal anesthesia, positional headaches, low blood pressure and backache were reported in 3% of patients, shivering was reported in 2%, and peripheral nerve symptoms, nausea, respiratory inadequacy and double vision were reported in < 1% of patients. Many of these observations may be related to local anesthetic techniques, with or without a contribution from the local anesthetic. Neurologic effects seen following spinal anesthesia include paresthesias, weakness and paralysis of lower extremities, low blood pressure, high or total spinal block, urinary retention, headache, back pain, septic meningitis, meningismus, arachnoiditis, shivering, cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid. Persistent motor, sensory, and/or autonomic (sphincter control) deficit of lower spinal segments with slow (several months) or incomplete recovery has been reported rarely.Lidocaine Hydrochloride 5% and Dextrose 7.5% Injection Solution package insert. Lake Forest, IL: Hospira, Inc.; 2010 Feb. Following spinal administration with lidocaine 5% with Dextrose, transient neuropathic pain, developing in the buttocks and radiating to the lateral thighs and calves may be seen. Complete resolution of symptoms usually takes place within 3 days but may persist for up to 2 months. Nausea occurred in 2% of patients who were treated with the lidocaine intradermal injection system during clinical trials.Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system package insert. Las Vegas, NV: 7T Pharma LLC; 2018 Nov.
Cardiac effects of local anesthetics such as lidocaine are due to the interference of conduction within the myocardium. Cardiac effects are seen at very high systemic doses and usually occur after the onset of CNS toxicity. Lidocaine-induced adverse cardiovascular effects include myocardial depression, sinus bradycardia, hypotension, cardiovascular collapse, and cardiac arrest. These effects typically occur with high plasma drug concentrations but have occurred with smaller doses in rare instances. Cardiovascular and CNS side effects resulting from lidocaine administration should be treated with general supportive physiologic measures such as oxygen therapy, assisted ventilation, and IV fluids. Monitor blood pressure and the electrocardiogram during intravenous lidocaine administration. If cardiovascular side effects such as hypotension, arrhythmia exacerbation, or excessive depression of cardiac conduction occur (e.g., prolonged PR interval or widened QRS complex), discontinue lidocaine administration and re-evaluate treatment options.Lidocaine hydrochloride injection solution package insert. Schaumburg, IL: APP Pharmaceuticals, LLC; 2010 Apr.Xylocaine (lidocaine hydrochloride topical solution 4%) package insert. Schaumburg, IL: APP Pharmaceuticals; 2009 Mar.Lidocaine Hydrochloride Oral Topical Solution (Viscous) 2% package insert. Lake Zurich, IL: Fresenius Kabi, Inc.; 2014 Sep.Lidocaine Ointment 5% package insert. Melville, NY: E. Fougera & Co.; 2007 Sept.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov.Xylocaine (lidocaine HCl) 2% Jelly package insert. Schaumburg, IL: APP Pharmaceuticals, LLC; 2008 Jun. Combining lidocaine with a vasoconstrictor increases the likelihood of producing anxiety, palpitations, dizziness, headache, restlessness, tremor, angina, and hypertension.
Local anesthetics generally are known to cross the placenta. For obstetric use, fetal heart rate should be monitored continuously because fetal bradycardia has occurred with high plasma levels of lidocaine. Maternal hypotension can result from regional anesthesia. Patient position can alleviate this problem, and the injection should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Because of the profound motor blockade produced when used epidurally, lidocaine can cause decreased uterine contractility and further decrease maternal expulsive efforts.Lidocaine Hydrochloride 5% and Dextrose 7.5% Injection Solution package insert. Lake Forest, IL: Hospira, Inc.; 2010 Feb. Unintended fetal intracranial injection of local anesthetics has occurred from attempted pudendal or paracervical block. Failure to achieve adequate anesthesia with standard doses should arouse suspicion of intracranial or intravascular injections. Infants so affected often present with unexplained neonatal depression at birth and can develop seizures within 6 hours as a result of high serum concentrations. Fetal bradycardia and fetal acidosis have resulted from paracervical injections.
Systemic adverse reactions after appropriate application of topical or transdermal lidocaine are unlikely because of the small amount of lidocaine absorbed. The skin at the site of treatment may develop erythema, swelling, or dysesthesia (abnormal sensation).Lidocaine hydrochloride 3% cream package insert. Port St. Joe, FL: Kylemore Pharmaceuticals; 2009 Dec.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov. Application site reactions may occur during or immediately after treatment with the lidocaine transdermal patch. Blisters, ecchymosis, depigmentation (skin discoloration), skin erosion, exfoliation, flushing, skin irritation (including burning sensation and dermatitis), papules, petechiae, pruritus, or vesicles may develop on the skin at the site of application. These reactions are usually mild and transient resolving within a few minutes to hours.Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov.ZTlido (lidocaine topical system) package insert. San Diego, CA: Scilex Pharmaceuticals, Inc.; 2021 Apr. Preexisting inflammation or infection increases the risk of developing serious skin side effects. There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration of lidocaine.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov. Additionally, small doses of local anesthetics injected into the head and neck area may produce an adverse reaction similar to systemic toxicity after unintentional intravascular injection.Lidocaine hydrochloride injection solution package insert. Schaumburg, IL: APP Pharmaceuticals, LLC; 2010 Apr. During adult and pediatric clinical trials of lidocaine injectable powder (Zingo), erythema (an injection site reaction) occurred in 53% to 67.3% of patients who received active drug, petechiae in 44% to 46.4% of patients, edema in 4.3% to 8% of patients, and pruritus in 1% to 9.4% of patients. Burning and venipuncture site hemorrhage occurred in 0.54% and 0.4% of adults, respectively. A total of 4% of pediatric patients experienced application site reactions that included ecchymosis, burning, pain, contusion, and hemorrhage.Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system package insert. Las Vegas, NV: 7T Pharma LLC; 2018 Nov.
Allergic and anaphylactoid reactions have been infrequently associated with lidocaine administration. Allergic reactions may manifest as cutaneous lesions, urticaria, edema, angioedema, bronchospasm, dermatitis, dyspnea, laryngospasm, pruritus, or anaphylactic shock. Allergic reactions may occur as a result of sensitivity either to local anesthetic agents or to other components in the formulation. The detection of sensitivity by skin testing is of questionable value. There have been no reports of cross-sensitivity between lidocaine and para-amino-benzoic acid derivatives (procaine, tetracaine, benzocaine, etc.).Lidoderm (lidocaine patch 5%) package insert. Malvern, PA: Endo Pharmaceuticals Inc.: 2018 Nov.Lidocaine hydrochloride injection solution package insert. Schaumburg, IL: APP Pharmaceuticals, LLC; 2010 Apr.Xylocaine (lidocaine hydrochloride topical solution 4%) package insert. Schaumburg, IL: APP Pharmaceuticals; 2009 Mar.Lidocaine Hydrochloride Oral Topical Solution (Viscous) 2% package insert. Lake Zurich, IL: Fresenius Kabi, Inc.; 2014 Sep.Lidocaine Ointment 5% package insert. Melville, NY: E. Fougera & Co.; 2007 Sept.Xylocaine (lidocaine HCl) 2% Jelly package insert. Schaumburg, IL: APP Pharmaceuticals, LLC; 2008 Jun.Lidocaine Hydrochloride Topical Solution 4% package insert. Morton Grove, IL: Morton Grove Pharmaceuticals, Inc.; 2006 Oct.ZTlido (lidocaine topical system) package insert. San Diego, CA: Scilex Pharmaceuticals, Inc.; 2021 Apr.
Methemoglobinemia has been reported with local anesthetic use. Signs and symptoms of methemoglobinemia may occur immediately or may be delayed some hours after local anesthetic exposure and are characterized by cyanotic skin discoloration and abnormal coloration of the blood. Other symptoms may include headache, rapid heart rate, shortness of breath, dizziness, and drowsiness. Since methemoglobin concentrations may continue to rise, immediately discontinue lidocaine to avoid serious central nervous system and cardiovascular adverse events including seizures, coma, arrhythmias, and death. Depending on the severity of symptoms, patients may require supportive care, such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.Karim A, Ahmed S, Siddiqui R, et al. Methemoglobinemia complicating topical lidocaine used during endoscopic procedures. Am J Med 2001;111:150-3.Weiss LD, Generalovinch T, Heller MB, et al. Methemoglobin levels following intravenous lidocaine administration. Ann Emerg Med 1987;16:323-5.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov.
Local anesthetics such as lidocaine administered by a continuous infusion to a joint space may cause chondrolysis (necrosis and destruction of cartilage). The FDA has received 35 reports of chondrolysis in patients given continuous intra-articular infusions of local anesthetics with elastomeric infusion devices to control post-surgical pain. Data suggest that the reported cases of chondrolysis are not associated with any single manufacturer of elastomeric infusion devices. In all but 1 patient, chondrolysis occurred after shoulder surgeries. The local anesthetics +/- epinephrine were infused for 48 to 72 hours directly into the intra-articular space using an elastomeric pump. The most commonly reported site of infusion was the glenohumeral (glenoid) space (46%), and bupivacaine was at least 1 of the local anesthetics used in all 35 cases. Joint pain, stiffness, and loss of motion were reported as early as the second month after infusion receipt. Chondrolysis was diagnosed a median of 8.5 months after the infusion. In more than half of these reports, the patients required additional surgery including arthroscopy or arthroplasty. In addition to the 35 bupivicaine-related cases, the FDA has received four additional reports of chondrolysis in patients administered continuous intra-articular infusions of lidocaine in the shoulder. It is not known which specific factor or combination of factors contributed to the development of chondrolysis. The infused local anesthetic drugs, the device materials, and/or other sources may have resulted in the development of chondrolysis. In vitro data do suggest that bupivacaine, lidocaine, and ropivacaine cause chondrolysis.Piper SL, Kim HT. Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am. 2008;90(5):986-91.Dragoo JL, Kortokova T, Kanwar R, Wood B. The effect of local anesthetics administered via pain pump on chondrocyte viability. Am J Sports Med. 2008;36(8):1484-8. Local anesthetics are not indicated for continuous intra-articular postoperative infusions or for use with infusion devices such as elastomeric pumps. Health care professionals are advised to NOT use elastomeric infusion devices for continuous intra-articular infusion of local anesthetics after orthopedic surgery. The FDA is requiring the drug manufacturers to update their product labels to warn healthcare professionals about the reported cases of chondrolysis after continuous intra-articular infusion with local anesthetics. The FDA is also requiring the manufacturers of pumps that may be used to infuse local anesthetics such as elastomeric infusion devices to have similar warnings for their products. Of importance, single intra-articular injections of local anesthetics in orthopedic procedures have been used for many years without any reported occurrence of chondrolysis. If a patient has received a continuous intra-articular postoperative infusion of a local anesthetic, monitor the patient for the emergence of the signs and symptoms of chondrolysis such as joint pain, stiffness, and loss of motion. Also, instruct the patient to report any such symptoms. The appearance of these symptoms can be variable and may begin two or more months after surgery.Xylocaine (lidocaine injection), Xylocaine (lidocaine and epinephrine injection) package insert. Lake Zurich, IL: Fresenius Kabi; 2018 Nov.Lidocaine Hydrochloride 5% and Dextrose 7.5% Injection Solution package insert. Lake Forest, IL: Hospira, Inc.; 2010 Feb.
Systemic adverse reactions after appropriate application of lidocaine ophthalmic gel are unlikely because of the small amount of lidocaine absorbed. After instillation of lidocaine ophthalmic gel, the most common reported side effects included conjunctival hyperemia, corneal epithelial changes, headache, and ocular irritation (burning upon instillation). Lidocaine ophthalmic gel, when used over a prolonged period, may cause permanent corneal opacification and ulceration leading to visual impairment.Akten (lidocaine hcl) ophthalmic gel package insert. Lake Forest, IL: Akorn, Inc.; 2012 Dec.
Drugs used to administer anesthesia have been associated with malignant hyperthermia. Although it is unknown whether local anesthetics, such as lidocaine, trigger this reaction, it is recommended that a standard protocol for management be available when lidocaine is administered in hospital environments. Early unexplained symptoms such as tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature elevation. Successful management includes prompt discontinuation of suspected triggering agents and institution of treatment.Lidocaine Hydrochloride 5% and Dextrose 7.5% Injection Solution package insert. Lake Forest, IL: Hospira, Inc.; 2010 Feb.
Phenylephrine HCl
Phenylephrine is a powerful vasoconstrictor, and parenteral administration causes a rise in systolic and diastolic pressures (i.e., hypertension), which may be accompanied by myocardial ischemia (i.e., angina) and/or marked reflex sinus bradycardia and AV block. An increased workload on the heart increases the risk of heart failure. Headache may be a sign of hypertension that can be relieved by administration of an alpha-adrenergic blocking agent (e.g., phentolamine). In general, geriatric patients are more susceptible than younger adults to a reduction in cardiac output following sinus bradycardia.
Contact dermatitis has been associated with phenylephrine, with cross-sensitivity to ephedrine.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.
Nervous system adverse reactions associated with phenylephrine therapy, especially parenteral routes of administration, include anxiety, excitability, paresthesias, tremor, headache, and restlessness.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.
Nausea, vomiting, and abdominal pain have been reported with the injectable formulation of phenylephrine.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun. Mild nausea or stomach upset may occur with non-prescription oral use at usual doses for congestion, but such adverse effects are not frequent. Ischemic colitis (bowel ischemia) has been rarely associated with the use of sympathomimetics, even oral phenylephrine, and may present with symptoms of abdominal pain and bloody diarrhea. Colitis may result from reversible splanchnic arterial vasoconstriction.Ward PW, Shaneyfelt TM, Roan RM. Acute ischaemic colitis associated with oral phenylephrine decongestant use. BMJ Case Rep. 2014 Jun 3;2014.
Dyspnea, pulmonary edema, and rales have been reported with the use of injectable phenylephrine.Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.Vazculep (phenylephrine) Inj package insert. Chesterfield, Mo: Eclat Pharmaceuticals; 2014 Jun.
Prilocaine
Like all local anesthetics, prilocaine can produce significant CNS toxicity when high serum concentrations are achieved. Neurologic reactions appear to be dose-related. Rapid absorption or accidental intravascular injection may lead to high plasma concentrations with subsequent reactions. CNS effects may be depressive or excitatory. Observed effects include dizziness or lightheadedness, anxiety or nervousness, euphoria, restlessness, confusion, drowsiness, tinnitus, blurred vision, twitching, nausea, vomiting, tremor, sensations of heat, cold, or numbness, and convulsions or seizures. Drowsiness can happen early following administration, which may lead to unconsciousness, respiratory depression, and respiratory arrest. Persistent paresthesias and swelling of the lips have been reported with use; these conditions may last weeks to > 1 year. Seizures can be treated with a slow infusion of IV benzodiazepines, although this should be done cautiously because benzodiazepines are also CNS depressants.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov.
Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal changes in cardiac conduction, excitability, refractoriness, and contractility. If a higher blood concentration of prilocaine is achieved due to inadvertent intravascular administration or repeated doses, depression of cardiac excitability and contractility may cause decreases in cardiac output, total peripheral resistance, and mean arterial pressure. Bradycardia, hypotension, arrhythmia exacerbation, and cardiovascular collapse leading to cardiac arrest may occur. A vasovagal reaction, particularly if the patient is in an upright position, or the drug itself may contribute to depressive cardiovascular effects. Other possible adverse cardiovascular effects associated with intravascular administration or high blood concentrations of local anesthetics include AV block, angina, QT prolongation, PR prolongation, palpitations, and atrial fibrillation. CNS-mediated cardiac effects in addition to blockade of sodium, potassium, and calcium channels within the heart may be responsible for some adverse cardiac effects. Symptoms of local anesthetic CNS toxicity appear to occur before cardiotoxic effects. Cardiovascular side effects resulting from prilocaine administration should be treated with general supportive physiologic measures, such as oxygen therapy, assisted ventilation, and IV fluids.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov.Scott DB, Lee A, Fagan D, et al. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989;69:563-9.Bardsley H, Gristwood R, Baker H, et al. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998;46:245-9.Knudsen K, Beckman Suurkula M, Blomberg S, et al. Central nervous and cardiovascular effects of iv infusions of ropivacaine, bupivacaine, and placebo in volunteers. Br J Anesth 1997;78:507-14.
Methemoglobinemia has been reported with local anesthetic use. Signs and symptoms of methemoglobinemia may occur immediately or may be delayed some hours after local anesthetic exposure and are characterized by cyanotic skin discoloration and abnormal coloration of the blood. Other symptoms may include headache, rapid heart rate, shortness of breath, dizziness, and drowsiness. Since methemoglobin concentrations may continue to rise, immediately discontinue prilocaine to avoid serious central nervous system and cardiovascular adverse events including seizures, coma, arrhythmias, and death. Depending on the severity of symptoms, patients may require supportive care, such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov.
Transient burning can occur at the injection site of prilocaine. Preexisting inflammation or infection increases the risk of developing serious skin side effects. Patients should be monitored for an injection site reaction.
Allergic reactions to prilocaine are characterized by skin rash (unspecified), urticaria, edema, pruritus, and anaphylactoid reactions. Sensitivity to prilocaine is rare; if reactions occur they should be managed by conventional means.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov.
Tetracaine
Tetracaine, like all local anesthetics, can produce significant CNS toxicity, particularly when high serum concentrations are achieved from rapid absorption, excessive dosage, or accidental intravascular injection. Tetracaine or other local anesthetic-induced CNS toxicity usually presents with symptoms of a CNS stimulation such as anxiety, apprehension, restlessness, nervousness, disorientation, confusion, dizziness, tinnitus, blurred vision, tremor, and/or seizures. Subsequently, depressive symptoms may occur including drowsiness, respiratory arrest, or coma. In some patients the symptoms of CNS toxicity may be minor and transient. Other reported effects include nausea/vomiting, chills, and miosis. CNS side effects resulting from local anesthetic administration, such as respiratory depression should be treated with general supportive physiologic measures. Seizures may be treated with benzodiazepines, although this should be done cautiously as benzodiazepines are also CNS depressants.Citanest Plain Dental (prilocaine) injection package insert. York, PA: AstraZeneca; 2018 Nov. Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun.
Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal changes in cardiac conduction, excitability, refractoriness, and contractility. If a higher blood concentration is achieved due to inadvertent intravascular administration or repeated doses, depression of cardiac excitability and contractility may cause decreases in cardiac output, total peripheral resistance, and mean arterial pressure. Bradycardia, hypotension, arrhythmia exacerbation, and cardiovascular collapse leading to cardiac arrest may occur. CNS-mediated cardiac effects in addition to blockade of sodium, potassium, and calcium channels within the heart may be responsible for some adverse cardiac effects. Other possible adverse cardiovascular effects associated with intravascular administration or high plasma concentrations of local anesthetics include angina, AV block, QT prolongation, PR prolongation, atrial fibrillation, and palpitations. Maternal seizures and cardiovascular collapse may occur following paracervical block in early pregnancy (i.e., as anesthesia for elective abortion) due to rapid systemic absorption. Symptoms of local anesthetic CNS toxicity appear to occur before cardiotoxic effects. Cardiovascular side effects resulting from tetracaine administration should be treated with general supportive physiologic measures, such as oxygen therapy, assisted ventilation, and IV fluids.Scott DB, Lee A, Fagan D, et al. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989;69:563-9. Bardsley H, Gristwood R, Baker H, et al. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998;46:245-9. Knudsen K, Beckman Suurkula M, Blomberg S, et al. Central nervous and cardiovascular effects of iv infusions of ropivacaine, bupivacaine, and placebo in volunteers. Br J Anesth 1997;78:507-14. Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun.
Neurologic effects seen following spinal anesthesia with agents like tetracaine include paresthesias, weakness and muscle paralysis of lower extremities, hypotension, high or total spinal block, urinary retention, urinary incontinence, fecal incontinence, headache, back pain, septic meningitis, meningismus, arachnoiditis, shivering, cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid, and loss of perineal sensation and sexual function. Persistent motor, sensory, and/or autonomic (sphincter control) deficit of lower spinal segments with slow (several months) or incomplete recovery has been reported rarely.Carbocaine (mepivacaine hydrochloride) package insert. Lake Forest, IL: Hospira, Inc.; 2018 Nov. Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun.
Transient burning may occur at the injection site. Pre-existing inflammation or infection increases the risk of developing serious skin side-effects. Patients should be monitored for an injection site reaction after tetracaine administration.Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun.
Reactions such as urticaria, edema, pruritus, or other cutaneous lesions and symptoms have been observed with tetracaine use; these reactions may be due to hypersensitivity, idiosyncrasy, or diminished tolerance. Anaphylaxis or other anaphylactoid reactions have been reported. Anaphylactoid-type reactions are usually not dose-related.Tetracaine HCl Injection package insert. Lake Forest, IL: Akorn, Inc.; 2016 Jun. Tetracaine may be more likely than other topical anesthetics to cause topical contact reactions including, skin rash (unspecified), mucous membrane irritation, erythema, pruritus, urticaria, burning, stinging, edema or tenderness.
Tetracaine ophthalmic preparations, when used over a prolonged period, may cause severe keratitis, delayed corneal healing and permanent corneal opacification and scarring leading to visual impairment. An immediate-type allergic reaction characterized by acute diffuse epithelial keratitis with filament formation and sloughing of large areas of necrotic epithelium, diffuse stromal edema, iritis, and descemetitis has been reported. The drug may also produce acute ocular pain and ocular irritation (burning, stinging, or erythema).Tetracaine hydrochloride ophthalmic solution. Tampa, FL: Bausch and Lomb; 2022 Feb.
During labor and obstetric delivery, local anesthetics such as tetracaine can cause varying degrees of maternal, fetal, and neonatal toxicities. The potential for toxicity is related to the procedure performed, the type and amount of drug used, and the technique of administration. Fetal heart rate should be monitored continuously because fetal bradycardia may occur in patients receiving tetracaine anesthesia and may be associated with fetal acidosis. Maternal hypotension can result from regional anesthesia; patient position can alleviate this problem. The injection should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Spinal tetracaine may cause decreased uterine contractility or maternal expulsion efforts and alter the forces of parturition.Novocain (procaine hydrochloride injection, USP) package insert. Lake Forest, IL: Hospira, Inc.; 2004 Nov.
Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.
