Sensorcaine

Name: Sensorcaine

Side Effects of Sensorcaine

Serious side effects have been reported with bupivacaine. See the “Bupivacaine Precautions” section.

Common side effects of bupivacaine include the following:

  • Nausea
  • Constipation
  • Vomiting
  • Chills

This is not a complete list of bupivacaine side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Sensorcaine Precautions

Serious side effects have been reported with bupivacaine including the following:

  • Central nervous system reactions. Tell your healthcare provider right away if you have some or all of the following symptoms of central nervous system reactions.
    • Restlessness, anxiety, dizziness, ringing in the ears, blurred vision, or tremors
    • Depression
    • Drowsiness or loss of consciousness
    • Nausea, vomiting, chills, or constriction of the pupils
  • Cardiovascular system reactions. Tell your healthcare provider right away if you have some or all of the following symptoms of cardiovascular system reactions.
    • Decreased blood pressure
    • Decreased heart rate
    • Ventricular arrhythmias
    • Cardiac arrest
  • Allergic-type reactions. Tell your healthcare provider right away if you have some or all of the following symptoms of allergic-type reactions.
    • Itching, hives, and redness
    • Swelling of the throat or face
    • Increased heart rate
    • Sneezing
    • Nausea
    • Vomiting
    • Dizziness
    • Loss of consciousness
    • Excessive sweating
    • Elevated temperature or fever
  • Neurologic reactions. Tell your healthcare provider right away if you have some or all of the following symptoms of neurologic reactions.
    • Decreased heart rate
    • Urinary retention
    • Fecal and urinary incontinence
    • Persistent anesthesia
    • Tingling in the extremities
    • Weakness
    • Paralysis of the lower extremities
    • Headache
    • Backache
    • Septic meningitis

 

Bupivacaine can cause drowsiness, dizziness, and blurred vision. Do not drive or operate heavy machinery until you know how bupivacaine affects you.

 

Do not take bupivacaine if you:

  • are allergic to bupivacaine or to any of its ingredients

Bupivacaine injection is contraindicated in obstetrical paracervical block anesthesia.

Sensorcaine Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your weight

The dose, frequency, and route of administration will vary, depending on the indication for use.

How is Sensorcaine (bupivacaine)given?

Bupivacaine is injected through a needle directly into or near the area to be numbed. You will receive this injection in a dental or hospital setting.

For an epidural, bupivacaine is given as an injection through a needle placed into an area of your middle or lower back near your spine.

For a dental procedure, bupivacaine is injected directly into the mouth near the tooth or teeth your dentist will be working on.

Your breathing, blood pressure, oxygen levels, or other vital signs will be watched closely while you are receiving bupivacaine.

Some epidural numbing medications can have long-lasting or permanent effects on certain body processes such as sexual function, bowel or bladder control, and movement or feeling in your legs or feet. Talk with your doctor about your specific risk of nerve damage from bupivacaine.

How is this medicine (Sensorcaine) best taken?

Use Sensorcaine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as a shot.
  • Your doctor will give this medicine.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Sensorcaine Description

Sensorcaine® (bupivacaine HCl) injections are sterile isotonic solutions that contain a local anesthetic agent with and without epinephrine (as bitartrate) 1:200,000 and are administered parenterally by injection.  See INDICATIONS AND USAGE for specific uses.  Solutions of bupivacaine HCl may be autoclaved if they do not contain epinephrine.

Sensorcaine injections contain bupivacaine HCl which is chemically designated as 2-piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate and has the following structure:

Epinephrine is (-)-3,4-Dihydroxy-α [(methylamino)methyl] benzyl alcohol.  It has the following structural formula:

The pKa of bupivacaine (8.1) is similar to that of lidocaine (7.86).  However, bupivacaine possesses a greater degree of lipid solubility and is protein bound to a greater extent than lidocaine.

Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics.  It is a homologue of mepivacaine and is chemically related to lidocaine.  All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group.  They differ in this respect from the procaine-type local anesthetics, which have an ester linkage.

Dosage forms listed as Sensorcaine-MPF indicates single dose solutions that are Methyl Paraben Free (MPF).

Sensorcaine-MPF is a sterile isotonic solution containing sodium chloride.  Sensorcaine in multiple dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative.  The pH of these solutions is adjusted to between 4.0 and 6.5 with sodium hydroxide and/or hydrochloric acid.

Sensorcaine-MPF with Epinephrine 1:200,000 (as bitartrate) is a sterile isotonic solution containing sodium chloride.  Each mL contains bupivacaine hydrochloride and 0.005 mg epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid (anhydrous) as stabilizer.  Sensorcaine with Epinephrine 1:200,000 (as bitartrate) in multiple dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative.  The pH of these solutions is adjusted to between 3.3 to 5.5 with sodium hydroxide and/or hydrochloric acid.  Filled under nitrogen.

Note: The user should have an appreciation and awareness of the formulations and their intended uses (see DOSAGE AND ADMINISTRATION).

Sensorcaine - Clinical Pharmacology

Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential.  In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers.  Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.

Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems (CNS).  At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal.  However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and cardiac arrest, sometimes resulting in fatalities.  In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.  Recent clinical reports and animal research suggest that these cardiovascular changes are more likely to occur after unintended intravascular injection of bupivacaine.  Therefore, incremental dosing is necessary.

Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression, or both. Apparent central stimulation is manifested as restlessness, tremors and shivering progressing to convulsions, followed by depression and coma progressing ultimately to respiratory arrest. However, the local anesthetics have a primary depressant effect on the medulla and on higher centers.  The depressed stage may occur without a prior excited state.

Pharmacokinetics

The rate of systemic absorption of local anesthetics is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution.  A dilute concentration of epinephrine (1:200,000 or 5 mcg/mL) usually reduces the rate of absorption and peak plasma concentration of bupivacaine, permitting the use of moderately larger total doses and sometimes prolonging the duration of action.

The onset of action with bupivacaine is rapid and anesthesia is long lasting.  The duration of anesthesia is significantly longer with bupivacaine than with any other commonly used local anesthetic.  It has also been noted that there is a period of analgesia that persists after the return of sensation, during which time the need for strong analgesics is reduced.

The onset of action following dental injections is usually 2 to 10 minutes and anesthesia may last two or three times longer than lidocaine and mepivacaine for dental use, in many patients up to 7 hours.  The duration of anesthetic effect is prolonged by the addition of epinephrine 1:200,000.

Local anesthetics are bound to plasma proteins in varying degrees.  Generally, the lower the plasma concentration of drug the higher the percentage of drug bound to plasma proteins.

Local anesthetics appear to cross the placenta by passive diffusion.  The rate and degree of diffusion is governed by (1) the degree of plasma protein binding, (2) the degree of ionization, and (3) the degree of lipid solubility.  Fetal/maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding, because only the free, unbound drug is available for placental transfer.  Bupivacaine with a high protein binding capacity (95%) has a low fetal/maternal ratio (0.2 to 0.4).  The extent of placental transfer is also determined by the degree of ionization and lipid solubility of the drug.  Lipid soluble, nonionized drugs readily enter the fetal blood from the maternal circulation.

Depending upon the route of administration, local anesthetics are distributed to some extent to all body tissues, with high concentrations found in highly perfused organs such as the liver, lungs, heart, and brain.

Pharmacokinetic studies on the plasma profile of bupivacaine after direct intravenous injection suggest a three-compartment open model.  The first compartment is represented by the rapid intravascular distribution of the drug.  The second compartment represents the equilibration of the drug throughout the highly perfused organs such as the brain, myocardium, lungs, kidneys, and liver.  The third compartment represents an equilibration of the drug with poorly perfused tissues, such as muscle and fat.  The elimination of drug from tissue distribution depends largely upon the ability of binding sites in the circulation to carry it to the liver where it is metabolized.

After injection of Sensorcaine (bupivacaine HCl) for caudal, epidural, or peripheral nerve block in man, peak levels of bupivacaine in the blood are reached in 30 to 45 minutes, followed by a decline to insignificant levels during the next 3 to 6 hours.

Various pharmacokinetic parameters of the local anesthetics can be significantly altered by the presence of hepatic or renal disease, addition of epinephrine, factors affecting urinary pH, renal blood flow, the route of drug administration, and the age of the patient.  The half-life of bupivacaine in adults is 2.7 hours and in neonates 8.1 hours.

In clinical studies, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger patients.  Elderly patients also exhibited higher peak plasma concentrations following administration of this product.  The total plasma clearance was decreased in these patients.

Amide-type local anesthetics such as bupivacaine are metabolized primarily in the liver via conjugation with glucuronic acid.  Patients with hepatic disease, especially those with severe hepatic disease, may be more susceptible to the potential toxicities of the amide-type local anesthetics. Pipecoloxylidine is the major metabolite of bupivacaine.

The kidney is the main excretory organ for most local anesthetics and their metabolites.  Urinary excretion is affected by urinary perfusion and factors affecting urinary pH.  Only 6% of bupivacaine is excreted unchanged in the urine.

When administered in recommended doses and concentrations, Sensorcaine (bupivacaine HCl) does not ordinarily produce irritation or tissue damage and does not cause methemoglobinemia.

Warnings

 THE 0.75% CONCENTRATION OF Sensorcaine INJECTION IS NOT RECOMMENDED FOR OBSTETRICAL ANESTHESIA.  THERE HAVE BEEN REPORTS OF CARDIAC ARREST WITH DIFFICULT RESUSCITATION OR DEATH DURING USE OF BUPIVACAINE FOR EPIDURAL ANESTHESIA IN OBSTETRICAL PATIENTS.  IN MOST CASES, THIS HAS FOLLOWED USE OF THE 0.75% CONCENTRATION.  RESUSCITATION HAS BEEN DIFFICULT OR IMPOSSIBLE DESPITE APPARENTLY ADEQUATE PREPARATION AND APPROPRIATE MANAGEMENT.  CARDIAC ARREST HAS OCCURRED AFTER CONVULSIONS RESULTING FROM SYSTEMIC TOXICITY, PRESUMABLY FOLLOWING UNINTENTIONAL INTRAVASCULAR INJECTION.  THE 0.75% CONCENTRATION SHOULD BE RESERVED FOR SURGICAL PROCEDURES WHERE A HIGH DEGREE OF MUSCLE RELAXATION AND PROLONGED EFFECT ARE NECESSARY.

LOCAL ANESTHETICS SHOULD ONLY BE EMPLOYED BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES WHICH MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED, AND THEN ONLY AFTER INSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY RESUSCITATIVE EQUIPMENT, AND THE PERSONNEL RESOURCES NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES (see also ADVERSE REACTIONS, PRECAUTIONS,  and OVERDOSAGE).  DELAY IN PROPER MANAGEMENT OF DOSE-RELATED TOXICITY, UNDERVENTILATION FROM ANY CAUSE AND/OR ALTERED SENSITIVITY MAY LEAD TO THE DEVELOPMENT OF ACIDOSIS, CARDIAC ARREST AND, POSSIBLY, DEATH.

Local anesthetic solutions containing antimicrobial preservatives, i.e., those supplied in multiple-dose vials, should not be used for epidural or caudal anesthesia because safety has not been established with regard to intrathecal injection, either intentionally or unintentionally, of such preservatives.

Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are not associated with these findings. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.

It is essential that aspiration for blood or cerebrospinal fluid (where applicable) be done prior to injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or subarachnoid injection.  However, a negative aspiration does not ensure against an intravascular or subarachnoid injection.

Bupivacaine with Epinephrine 1:200,000 or other vasopressors should not be used concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur.  Likewise, solutions of bupivacaine containing a vasoconstrictor, such as epinephrine, should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result.

Until further experience is gained in pediatric patients younger than 12 years, administration of bupivacaine in this age group is not recommended.

Mixing or the prior or intercurrent use of any local anesthetic with bupivacaine cannot be recommended because of insufficient data on the clinical use of such mixtures.

There have been reports of cardiac arrest and death during the use of bupivacaine for intravenous regional anesthesia (Bier Block).  Information on safe dosages and techniques of administration of bupivacaine in this procedure is lacking. Therefore, bupivacaine is not recommended for use in this technique.

Sensorcaine with epinephrine 1:200,000 contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.  The overall prevalence of sulfite sensitivity in the general population is unknown and probably low.  Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.  Sensorcaine and Sensorcaine - MPF without epinephrine single dose vials do not contain sodium metabisulfite.

Overdosage

Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution (see ADVERSE REACTIONS, WARNINGS, and PRECAUTIONS).

Management of Local Anesthetic Emergencies

The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic injection. At the first sign of change, oxygen should be administered.

The first step in the management of systemic toxic reactions, as well as underventilation or apnea due to unintentional subarachnoid injection of drug solution, consists of  immediate  attention to the establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100% oxygen with a delivery system capable of permitting immediate positive airway pressure by mask. This may prevent convulsions if they have not already occurred.

If necessary, use drugs to control the convulsions.  A 50 mg to 100 mg bolus IV injection of succinylcholine will paralyze the patient without depressing the central nervous or cardiovascular systems and facilitate ventilation.  A bolus IV dose of 5 mg to 10 mg of diazepam or 50 mg to 100 mg of thiopental will permit ventilation and counteract central nervous system stimulation, but these drugs also depress central nervous system, respiratory, and cardiac function, add to postictal depression and may result in apnea.  Intravenous barbiturates, anticonvulsant agents, or muscle relaxants should only be administered by those familiar with their use.  Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated. Supportive treatment of circulatory depression may require administration of intravenous fluids, and when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine or epinephrine to enhance myocardial contractile force).

Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated after initial administration of oxygen by mask if difficulty is encountered in the maintenance of a patent airway, or if prolonged ventilatory support (assisted or controlled) is indicated.

Recent clinical data from patients experiencing local anesthetic-induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions.  These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.

If not treated immediately, convulsions with simultaneous hypoxia, hypercarbia, and acidosis plus myocardial depression from the direct effects of the local anesthetic may result in cardiac arrhythmias, bradycardia, asystole, ventricular fibrillation, or cardiac arrest.  Respiratory abnormalities, including apnea, may occur. Underventilation or apnea due to unintentional subarachnoid injection of local anesthetic solution may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted.  If cardiac arrest should occur, successful outcome may require prolonged resuscitative efforts.

The supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus.  Therefore during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels should be accomplished.

The mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL.  The intravenous and subcutaneous LD50 in mice is 6 mg/kg to 8 mg/kg and 38 mg/kg to 54 mg/kg respectively.

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