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Bupivacaine

FDA Drug Information • Also known as: Bupivacaine, Exparel

Brand Names
Bupivacaine, Exparel
Dosage Form
POWDER
Product Type
BULK INGREDIENT

Description

11. DESCRIPTION Bupivacaine liposome injectable suspension is a sterile, non-pyrogenic white to off-white preservative-free aqueous suspension consisting of multivesicular liposomes containing bupivacaine for infiltration and interscalene brachial plexus nerve block. Bupivacaine is present at a concentration of 13.3 mg/mL. After injection of bupivacaine liposome injectable suspension, bupivacaine is released from the multivesicular liposomes. Bupivacaine liposome injectable suspension is for infiltration or perineural use. Active Ingredient Bupivacaine is related chemically and pharmacologically to the amide-type local anesthetics. It is a homologue of mepivacaine and is related chemically 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. Chemically, bupivacaine is 1-butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide with a molecular weight of 288.4. Bupivacaine has the following structural formula: Bupivacaine Liposome Injectable Suspension The median diameter of the liposome particles in bupivacaine liposome injectable suspension ranges from 22 to 30 μm. The liposomes are suspended in a 0.9% Sodium Chloride Injection. Each vial contains bupivacaine at a nominal concentration of 13.3 mg/mL. Inactive ingredients and their nominal concentrations are: cholesterol, 4.7 mg/mL; 1, 2-dipalmitoyl-sn-glycero-3 phospho-rac-(1-glycerol) sodium salt (DPPG), 0.9 mg/mL; tricaprylin, 2.0 mg/mL; 1, 2-dierucoylphosphatidylcholine (DEPC), 8.2 mg/mL; and phosphoric acid to adjust pH. The pH of bupivacaine liposome injectable suspension is in the range of 5.8 to 7.4. Bupivacaine in bupivacaine liposome injectable suspension has different functional properties relative to those of the unencapsulated or nonlipid-associated bupivacaine products. Bupivacaine that is released from bupivacaine liposome...

What Is Bupivacaine Used For?

1. INDICATIONS AND USAGE Bupivacaine liposome injectable suspension is indicated to produce postsurgical: Local analgesia via infiltration in adults Regional analgesia via an interscalene brachial plexus nerve block in adults Limitations of Use The safety and effectiveness of bupivacaine liposome injectable suspension have not been established to produce postsurgical regional analgesia via other nerve blocks besides an interscalene brachial plexus nerve block. Bupivacaine liposome injectable suspension contains bupivacaine, an amide local anesthetic, and is indicated to produce postsurgical: Local analgesia via infiltration in adults ( 1 ). Regional analgesia via an interscalene brachial plexus nerve block in adults ( 1 ). Limitations of Use The safety and effectiveness of bupivacaine liposome injectable suspension have not been established to produce postsurgical regional analgesia via other nerve blocks besides an interscalene brachial plexus nerve block.

Dosage and Administration

2. DOSAGE AND ADMINISTRATION Bupivacaine liposome injectable suspension is for single administration only ( 2.1 ). Bupivacaine liposome injectable suspension is not substitutable with other bupivacaine products even if the strength is the same. Therefore, it is not possible to convert a dose from other bupivacaine products to a bupivacaine liposome injectable suspension dose and vice versa ( 2.1 , 2.5 ). Do not dilute bupivacaine liposome injectable suspension with water or other hypotonic solutions ( 2.1 ). The recommended dose of bupivacaine liposome injectable suspension for: Local infiltration in adults is up to a maximum dose of 266 mg. See Full Prescribing Information for guidance on dose selection ( 2.2 ). Interscalene brachial plexus nerve block in adults is 133 mg ( 2.3 ). For the nerve block, administer additional analgesics, which may include other immediate-release local anesthetics, as appropriate ( 2.3 ). See Full Prescribing Information for important preparation and administration instructions and compatibility considerations ( 2.4 , 2.5 ). 2.1 Important Dose, Preparation, and Administration Instructions Bupivacaine liposome injectable suspension is for single administration only. Bupivacaine liposome injectable suspension is not substitutable with other bupivacaine products even if the strength is the same. Therefore, it is not possible to convert a dose from other bupivacaine products to a bupivacaine liposome injectable suspension dose and vice versa. Do not dilute bupivacaine liposome injectable suspension with water or other hypotonic agents, as it will result in disruption of the liposomal particles. Do not administer bupivacaine liposome injectable suspension if it is suspected that the vial has been frozen or exposed to high temperature (greater than 40°C or 104°F) for an extended period. Inspect bupivacaine liposome injectable suspension visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer bupivacaine liposome injectable suspension if the product is discolored. Do not heat or autoclave before use. Do not filter during administration. 2.2 Recommended Dose for Local Analgesia via Infiltration Local Analgesia via Infiltration in Adults The recommended dose of bupivacaine liposome injectable suspension for local infiltration in adults is up to a maximum dose of 266 mg, and is based on the following factors: Size of the surgical site Volume required to cover the area Individual patient factors that may impact the safety of an amide local anesthetic As general guidance in selecting the proper bupivacaine liposome injectable suspension dose for local infiltration in adults, two examples are provided [ see Clinical Studies ( 14.2 )]. In adult patients undergoing: Bunionectomy, a total of 106 mg (8 mL) of bupivacaine liposome injectable suspension was administered, with 7 mL infiltrated into the tissues surrounding the osteotomy, and 1 mL infiltrated...

Side Effects (Adverse Reactions)

6. ADVERSE REACTIONS The following serious adverse reactions have been associated with bupivacaine hydrochloride in clinical trials and are described in greater detail in other sections of the labeling: Central Nervous System Reactions [ see Warnings and Precautions ( 5.1 ) ] Cardiovascular System Reactions [ see Warnings and Precautions ( 5.1 ) ] Allergic Reactions [ see Warnings and Precautions ( 5.1 ) ] Chondrolysis [ see Warnings and Precautions ( 5.1 ) ] Methemoglobinemia [ see Warnings and Precautions ( 5.1 ) ] Accidental intravascular injection [ see Warnings and Precautions ( 5.2 ) ] Adverse reactions reported with an incidence greater than or equal to 10% following bupivacaine liposome injectable suspension administration via: Infiltration in adults were nausea, constipation, and vomiting ( 6.1 ). Nerve block in adults were nausea, pyrexia, headache, and constipation ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact eVenus Pharmaceutical Laboratories, Inc. at 1-609-395-8625 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adverse Reactions Reported in All Local Infiltration Clinical Studies in Adults The safety of bupivacaine liposome injectable suspension (local administration into the surgical site) was evaluated in 10 randomized, double-blind, clinical studies (including Studies 1 and 2 [ see Clinical Studies ( 14.2 ) ]) that included 823 adult patients who had various surgical procedures. Patients were administered a bupivacaine liposome injectable suspension dose ranging from 66 to 532 mg (two times the maximum recommended dose of 266 mg). In these studies, following bupivacaine liposome injectable suspension administration, the: Most common adverse reactions (incidence greater than or equal to 10%) were nausea, constipation, and vomiting. Common adverse reactions (incidence greater than or equal to 2% to less than 10%) were pyrexia, dizziness, peripheral edema, anemia, hypotension, pruritus, tachycardia, headache, insomnia, postoperative anemia, muscle spasms, hemorrhagic anemia, back pain, somnolence, and procedural pain. Less common adverse reactions (incidence less than 2%) were chills, erythema, bradycardia, anxiety, urinary retention, pain, edema, tremor, postural dizziness, paresthesia, syncope, incision site edema, procedural hypertension, procedural hypotension, procedural nausea, muscular weakness, neck pain, generalized pruritus, pruritic rash, hyperhidrosis, cold sweat, urticaria, palpitations, sinus bradycardia, supraventricular extrasystoles, ventricular extrasystoles, ventricular tachycardia, hypertension, pallor, anxiety, confusional state, depression, agitation, restlessness, hypoxia, laryngospasm, apnea, respiratory depression, respiratory failure, increased body temperature, increased blood pressure (BP),decreased BP, decreased oxygen saturation, urinary incontinence, blurred vision, tinnitus, drug hypersensitivity, and hypersensitivity. Neurological and Cardiac Adverse Reactions In the bupivacaine liposome injectable suspension surgical site infiltration studies, following bupivacaine liposome injectable suspension administration adverse reactions with an incidence greater than or equal to 1% in the: Nervous System Disorders system organ class were dizziness (6.2%), headache (3.8%), somnolence (2.1%), hypoesthesia (1.5%), and lethargy (1.3%). Cardiac Disorders system organ class were tachycardia (3.9%) and bradycardia (1.6%). Adverse Reactions Reported in All Local Infiltration Placebo-Controlled Trials in Adults Adverse reactions with an incidence greater than or equal to 2% reported by adult patients in clinical studies who underwent a bunionectomy (Study 1) or hemorrhoidectomy (Study 2) [...

Drug Interactions

7. DRUG INTERACTIONS The toxic effects of local anesthetics are additive and concomitant use should be used with caution including monitoring for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [ See Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 ), and Overdosage ( 10 ) ]. Avoid additional use of local anesthetics within 96 hours following administration of bupivacaine liposome injectable suspension. Patients who are administered local anesthetics, including bupivacaine liposome injectable suspension, may be at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine Bupivacaine Bupivacaine HCl administered together with bupivacaine liposome injectable suspension may impact the pharmacokinetic and/or physicochemical properties of bupivacaine liposome injectable suspension, and this effect is concentration dependent. Therefore, bupivacaine HCl and bupivacaine liposome injectable suspension may be administered simultaneously in the same syringe, and bupivacaine HCl may be injected immediately before bupivacaine liposome injectable suspension as long as the ratio of the milligram dose of bupivacaine HCl solution to bupivacaine liposome injectable suspension does not exceed 1:2. Non-Bupivacaine Local Anesthetics Bupivacaine liposome injectable suspension should not be admixed with local anesthetics other than bupivacaine. Non-bupivacaine based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from bupivacaine liposome injectable suspension if administered together locally. The administration of bupivacaine liposome injectable suspension may follow the administration of lidocaine after a delay of 20 minutes or more. There are no data to support administration of other local anesthetics prior to administration of bupivacaine liposome injectable suspension. Other than bupivacaine as noted above, bupivacaine liposome injectable suspension should not be admixed with other drugs prior to administration. Water and Hypotonic Agents Do not dilute bupivacaine liposome injectable suspension with water or other hypotonic agents, as it will result in disruption of the liposomal particles. Lidocaine or other non-bupivacaine local anesthetics: Do not admix with bupivacaine liposome injectable suspension. Bupivacaine liposome injectable suspension may be...

Contraindications

4. CONTRAINDICATIONS Bupivacaine liposome injectable suspension is contraindicated in obstetrical paracervical block anesthesia [ see Use in Specific Populations ( 8.1 ) ]. While bupivacaine liposome injectable suspension has not been tested with this technique, the use of bupivacaine HCl with this technique has resulted in fetal bradycardia and death. Bupivacaine liposome injectable suspension is contraindicated in obstetrical paracervical block anesthesia ( 4 ).

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no studies conducted with bupivacaine liposome injectable suspension in pregnant women. In animal reproduction studies, embryo-fetal deaths were observed with subcutaneous administration of bupivacaine to rabbits during organogenesis at a dose equivalent to 1.6 times the maximum recommended human dose (MRHD) of 266 mg. Subcutaneous administration of bupivacaine to rats from implantation through weaning produced decreased pup survival at a dose equivalent to 1.5 times the MRHD [ see Data ]. Based on animal data, advise pregnant women of the potential risks to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Clinical Considerations Labor or Delivery Bupivacaine is contraindicated for obstetrical paracervical block anesthesia. While bupivacaine liposome injectable suspension has not been studied with this technique, the use of bupivacaine for obstetrical paracervical block anesthesia has resulted in fetal bradycardia and death. Bupivacaine can rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity [ See Clinical Pharmacology ( 12.3 )]. The incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function. Data Animal Data Bupivacaine hydrochloride was administered subcutaneously to rats and rabbits during the period of organogenesis (implantation to closure of the hard plate). Rat doses were 4.4, 13.3, and 40 mg/kg/day (equivalent to 0.2, 0.5 and 1.5 times the MRHD,...

Overdosage

10. OVERDOSAGE Clinical Presentation Acute emergencies from local anesthetics are generally related to high plasma concentrations encountered during therapeutic use of local anesthetics or to unintended intravascular injection of local anesthetic solution [ See Warnings and Precautions ( 5 ) and Adverse Reactions ( 6 )] . Signs and symptoms of overdose include CNS symptoms (perioral paresthesia, dizziness, dysarthria, confusion, mental obtundation, sensory and visual disturbances, and eventually convulsions) and cardiovascular effects (that range from hypertension and tachycardia to myocardial depression, hypotension, bradycardia, and asystole). Plasma levels of bupivacaine associated with toxicity can vary. Although concentrations of 2,500 to 4,000 ng/mL have been reported to elicit early subjective CNS symptoms of bupivacaine toxicity, symptoms of toxicity have been reported at levels as low as 800 ng/mL. Management of Local Anesthetic Overdose At the first sign of change, oxygen should be administered. The first step in the management of convulsions, as well as underventilation or apnea, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously. The clinician should be familiar, prior to the use of anesthetics, with these anticonvulsant drugs. Supportive treatment of circulatory depression may require...

How Supplied

16. HOW SUPPLIED/STORAGE AND HANDLING Bupivacaine liposome injectable suspension is a white to off-white milky aqueous suspension that is available in the following single-dose vials. 1.3% (133 mg/10 mL) (13.3 mg/mL) single-dose vial, (NDC 57884-3251-1) packaged in cartons of 10 (NDC 57884-3251-1) 1.3% (266 mg/20 mL) (13.3 mg/mL) single-dose vial, (NDC 57884-3252-1) packaged in cartons of 10 (NDC 57884-3252-1) Storage Store bupivacaine liposome injectable suspension vials refrigerated between 2° to 8°C (36° to 46°F). Bupivacaine liposome injectable suspension may be held at a controlled room temperature of 20° to 25°C (68° to 77°F) for up to 30 days in sealed, intact (unopened) vials. Do not re-refrigerate vials. Do not freeze or expose bupivacaine liposome injectable suspension to high temperatures (greater than 40°C or 104°F) for an extended period. Do not administer bupivacaine liposome injectable suspension if it is suspected of having been frozen or exposed to high temperatures. Do not use the vial if the stopper is bulging. Handling See Dosage and Administration ( 2.1 , 2.4 ) for important preparation instructions.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.