Bupivacaine-Dextrose (bupivacaine HCl in dextrose/PF)

Dosage of bupivacaine varies with the anesthetic procedure, degree of anesthesia required, surgical site, and individual patient response. The usual dosages should generally be reduced in geriatric, debilitated, or acutely ill patients and in patients with cardiac and/or hepatic disease. The lowest effective dose should be used.

Conventional bupivacaine hydrochloride preparations may be administered by local infiltration or by lumbar epidural (including caudal), peripheral, retrobulbar, sympathetic, or dental block. For spinal anesthesia, 0.75% bupivacaine hydrochloride in 8.25% dextrose is administered by subarachnoid injection. BUPivacaine liposomal injection (Exparel(R)) is administered by local infiltration or interscalene brachial plexus nerve block; the liposomal formulation should not be administered by epidural or intrathecal routes, and should not be used for other regional nerve blocks.

Local anesthetics, including bupivacaine, have been administered by continuous intra-articular infusion+ (e.g., for control of postoperative pain); however, such use has been associated with chondrolysis. (See Cautions: Musculoskeletal Effects in the Local Anesthetics, Parenteral, General Statement 72:00.) BUPivacaine should not be administered using the Bier block technique (IV regional anesthesia) due to the risk of cardiac arrest and death.

BUPivacaine solutions containing preservatives should not be used for epidural or caudal block. Partially used solutions that do not contain preservatives should be discarded.

The liposomal formulation is not bioequivalent to and should not be used interchangeably with other bupivacaine formulations.

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There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Local Anesthetics/Long-Acting Bupivacaine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use of other local anesthetics or use of other local anesthetics within 96 hours following long-acting bupivacaine may result in additive neurologic and cardiovascular effects. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also increase the risk of methemoglobinemia.(1,2) Non-liposomal bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally.(1)

CLINICAL EFFECTS: Concurrent or use of local anesthetics with 96 hours of use of long-acting bupivacaine may result in neurologic and cardiovascular toxicity. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also result in methemoglobinemia.(1,2) Non-liposomal bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally.(1)

PREDISPOSING FACTORS: Use of additional agents that are associated with methemoglobinemia may further increase the risk of methemoglobinemia.(1) Patients who are at increased risk of developing methemoglobinemia include those with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.(1)

PATIENT MANAGEMENT: Avoid the use of other local anesthetics within 96 hours following the administration of long-acting bupivacaine. In patients for whom use is required, monitor for neurologic and cardiovascular effects. Also monitor for methemoglobinemia with use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine.(1,2) Non-liposomal bupivacaine may be administered in the same syringe as bupivacaine liposomal or injected immediately before bupivacaine liposomal as long as the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Lidocaine may be administered 20 minutes or more prior to bupivacaine. It is unknown if other local anesthetics may be used without compromising the release characteristic of bupivacaine liposomal.(1)

DISCUSSION: Concurrent use of other local anesthetics or use of other local anesthetics within 96 hours following long-acting bupivacaine may result in additive neurologic and cardiovascular effects. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also increase the risk of methemoglobinemia.(1,2) Non-liposome bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally. Lidocaine may be administered 20 minutes or more prior to bupivacaine. It is unknown if other local anesthetics may be used without compromising the release characteristic of bupivacaine liposomal.(1)

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

• Methemoglobinemia
• Regional anesthesia for labor pain
• Severe hypotension
• Shock

• First degree atrioventricular heart block
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Second degree atrioventricular heart block

• Bradycardia
• Glucose-6-phosphate dehydrogenase (g6Pd) deficiency
• Hemolytic anemia from pyruvate kinase and g6PD deficiencies
• Severe hepatic disease

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Rare or Very Rare

• Acute respiratory failure
• Anaphylaxis
• Angioedema
• Bradycardia
• Cardiac arrhythmia
• Chondrolysis of articular cartilage
• CNS depression
• CNS toxicity
• Excitement
• Heart block
• Hemiparesis
• Hypertension
• Hypotension
• Methemoglobinemia
• Muscle fasciculation
• Myocardial dysfunction
• Paralysis
• Seizure disorder
• Tachycardia
• Unconsciousness
• Urticaria
• Vasodilation of blood vessels
• Ventricular arrhythmias

More Frequent

• Constipation
• Nausea
• Vomiting

Less Frequent

• Drowsy

Rare or Very Rare

• Blurred vision
• Chills
• Diplopia
• Dizziness
• Dysgeusia
• Erythema
• Fecal incontinence
• General weakness
• Miosis
• Muscle weakness
• Nervousness
• Oral hypoesthesia
• Paresthesia
• Pruritus of skin
• Skin rash
• Sneezing
• Symptoms of anxiety
• Tinnitus
• Tremor
• Urinary incontinence
• Urinary retention
• Visual changes

BUPivacaine shares the toxic potentials of the local anesthetics, and the usual precautions of local anesthetic therapy should be observed. (See Cautions in the Local Anesthetics, Parenteral, General Statement 72:00.)

Adverse effects of bupivacaine generally are limited when administered locally at the recommended dosages and routes. However, excessive plasma concentrations can lead to systemic toxicity manifesting principally as CNS and cardiovascular effects.

The 0.75% solution of bupivacaine hydrochloride is not recommended for obstetric anesthesia since use of this concentration for epidural anesthesia in obstetric patients has been associated with cardiac arrest with difficult resuscitation or death. Cardiac arrest has occurred after seizures resulting from systemic toxicity, apparently following inadvertent intravascular injection.

Some commercially available formulations of bupivacaine hydrochloride contain sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.

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