Liposomal bupivacaine (Exparel) is a long-acting anesthetic drug that is used to relieve post-surgical pain when injected directly into the surgical site.

Liposomal bupivacaine Uses:

• Postsurgical Analgesia:

  • Single-dose infiltration is done in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia.

Liposomal bupivacaine (Exparel) Dose in Adults:

Note: Bupivacaine (liposomal) is not bioequivalent to bupivacaine hydrochloride; dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) or vice versa is not possible.

Liposomal bupivacaine (Exparel) Dose in postsurgical Analgesia:

• Local anesthesia:

  • Infiltration: Single dose: Dose is based on the following
    • Surgical site size
    • The volume required to cover the area
    • Individual patient factors (maximum dose: 266 mg [20 mL])
  • General dosage guidance for bunionectomy and hemorrhoidectomy is given below:

• Bunionectomy:

  • In the tissues surrounding the osteotomy, 7 mL of undiluted bupivacaine (liposomal) infiltrated, and in the subcutaneous tissue of the surgical site, 1 mL of undiluted bupivacaine (liposomal) infiltrated (total dose = 106 mg [8 mL])

• Hemorrhoidectomy:

  • Around the anal sphincter, 30 mL of diluted bupivacaine (liposomal) (20 mL diluted with 10 mL NS) divided and infiltrated as 6 injections of 5 mL each (total dose = 266 mg [20 mL]).

Liposomal bupivacaine (Exparel) Dose in Regional analgesia:

• Interscalene brachial plexus nerve block: Single dose:
  • Total shoulder arthroplasty or rotator cuff repair: 133 mg (10 mL)

Use in Children:

Not indicated.

Pregnancy Risk Category: C

• Animal reproduction studies have seen adverse events.
• Bupivacaine crosses the placenta.
• It is not recommended for pregnant women.
• Contraindicated in obstetrical paracervical anesthesia. May cause bradycardia or death of the foetus.

Use during breastfeeding:

• Breast milk contains buprevacaine.
• These points are recommended by the manufacturer when deciding whether to continue breastfeeding or stop it during therapy.
  • Infant exposure is a risk
  • Breastfeeding is good for the infant
  • Mothers can reap the benefits of mother-to-child treatment

Dose in Kidney Disease:

No dosage adjustments have been provided in the manufacturer’s labeling; use cautiously; bupivacaine metabolism may be reduced in severe renal impairment and systemic exposure and the risk of adverse effects or toxicities may be increased.

Dose in Liver disease:

No dosage adjustments have been provided in the manufacturer’s labeling; use cautiously; bupivacaine metabolism may be reduced in severe hepatic impairment and systemic exposure and the risk of adverse effects or toxicities may be increased.

Common Side Effects of Liposomal bupivacaine (Exparel):

• Central nervous system:

  • Motor dysfunction

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Constipation

• Miscellaneous:

  • Fever

Less Common Side Effects of Liposomal bupivacaine (Exparel):

• Cardiovascular:

  • Hypertension
  • Hypotension
  • Procedural Hypotension
  • Tachycardia
  • Peripheral Edema
  • Sinus Tachycardia
  • Atrial Fibrillation
  • Bradycardia
  • Bundle Branch Block
  • Cardiac Arrhythmia
  • Deep Vein Thrombosis
  • Edema
  • First Degree Atrioventricular Block
  • Oxygen Saturation Decreased
  • Orthostatic Hypotension
  • Palpitations
  • Presyncope
  • Prolonged QT Interval On ECG
  • Sinus Bradycardia
  • Supraventricular Extrasystole
  • Syncope
  • Ventricular Premature Contractions
  • Ventricular Tachycardia

• Central Nervous System:

  • Insomnia
  • Procedural Pain
  • Headache
  • Dizziness
  • Confusion
  • Fatigue
  • Drowsiness
  • Hypoesthesia
  • Anxiety
  • Sensation Of Cold
  • Falling
  • Feeling Hot
  • Mobility Disorder
  • Sensation Disorder
  • Agitation
  • Chills
  • Delirium
  • Depression
  • Hyperthermia
  • Myasthenia
  • Pain
  • Paresthesia
  • Restlessness
  • Sedation
  • Lethargy

• Dermatologic:

  • Hyperhidrosis
  • Pruritus
  • Cellulitis
  • Diaphoresis
  • Erythema
  • Increased Wound Secretion
  • Pallor
  • Pruritic Rash
  • Skin Blister
  • Skin Rash
  • Urticaria

• Gastrointestinal:

  • Dysgeusia
  • Oral Hypoesthesia
  • Hiccups

• Genitourinary:

  • Urinary Retention
  • Dysuria
  • Urinary Incontinence

• Hematologic & Oncologic:

  • Acute Post Hemorrhagic Anemia
  • Anemia
  • Bruise
  • Hematoma
  • Leukocytosis
  • Postoperative Hematoma

• Hepatic:

  • Increased Liver Enzymes
  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Alanine Aminotransferase

• Hypersensitivity:

  • Fixed Drug Eruption
  • Hypersensitivity Reaction

• Infection:

  • Fungal Infection

• Local:

  • Localized Edema

• Neuromuscular & Skeletal:

  • Back Pain
  • Muscle Spasm
  • Muscle Twitching
  • Arthralgia
  • Asthenia
  • Joint Swelling
  • Laryngospasm
  • Musculoskeletal Pain
  • Neck Pain
  • Tremor

• Ophthalmic:

  • Blurred Vision
  • Decreased Visual Acuity

• Otic:

  • Auditory Impairment
  • Tinnitus

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Hypoxia
  • Apnea
  • Atelectasis
  • Cough
  • Dyspnea
  • Pulmonary Infiltrates
  • Pneumonia
  • Pulmonary Infection
  • Respiratory Depression
  • Respiratory Failure

• Miscellaneous:

  • Procedural Complications
  • Dehiscence

Contraindications to Liposomal bupivacaine (Exparel):

Anesthesia for obstetrical paracervical blocks

Warnings and precautions

• CNS effects

  • CNS effects, including excitation and/or depression, may cause convulsions, unconsciousness and/or respiratory arrest.
  • CNS effects can be caused by the following:
    • The total amount of medication taken
    • Route of administration
    • The patient's physical condition
  • After each injection, the patient should be closely monitored for any CNS-related changes.
  • Local anesthesia may also cause irreversible neurologic effects due to infiltration of soft tissues (persistent Anesthesia, Paresthesia Weakness, Paralysis).

• CNS toxicity:

  • Monitor the patient's consciousness after each local anesthetic injection.
  • The signs of CNS toxicities include restlessness, anxiety and lightheadedness.
  • Temporary motor and sensory loss can occur. It may last for up to five days.

• Cardiovascular toxicity:

  • Toxic concentrations can cause serious and fatal cardiovascular system reactions, such as decreased cardiac output, arterial blood pressure, ventricular arrhythmias and cardiac arrest.

• Hypersensitivity reactions

  • These include:
    • Allergy-type reactions include dizziness, hyperthermia, increased temperature, excessive sweating and nausea.
    • An allergy like symptoms (including severe hypotension, rare)
    • Cross-sensitivity between amide-type local anesthetics

• Infusion-related intra-articular chondrolysis

  • Continuous intra-articular injection of local anesthetics after arthroscopic surgery or other procedures is not permitted. Infusions chondrolysis, which occurs primarily in the shoulder joint, may require arthroplasty.

• Methemoglobinemia:

  • Methemoglobinemia has been reported in cases following the administration of local anesthetics.
  • In the case of clinically significant methemoglobinemia, immediate treatment is necessary.
  • After anesthesia exposure, there may be an immediate (or delayed) onset.
  • Patients in the following groups are more vulnerable and should be monitored closely for signs and symptoms such as cyanosis and headaches.
    • Patients suffering from G6PD deficiency
    • Congenital and idiopathic methemoglobinemia
    • Cardiac and pulmonary compromise
    • Exposition to oxidizing agents and their metabolites
    • Infants younger than 6 months

• Respiratory arrest

  • After the administration of local anesthetics, a sudden respiratory arrest can occur (rarely).

• Seizures:

  • Convulsions due systemic toxicities leading to cardiac arrest can be caused by local anesthesia.

• Cardiovascular disease

  • Patients with heart disease should be cautious; bupivacaine can prolong AV conduction, which causes functional changes that are less compensable in patients with impaired cardiovascular function.

• Hepatic impairment

  • Patients with severe hepatic impairment should be cautious. There may be an increased risk of toxicities in these patients.

• Renal impairment

  • Patients with impaired renal function should be cautious; there could be an increased risk of toxicities.

Liposomal bupivacaine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Cardiovascular status
• Respiratory status (adequacy of ventilation)
• State of consciousness
• Signs of CNS toxicity
• Pain relief

How to administer Liposomal bupivacaine (Exparel)?

• It may be administered undiluted or diluted. Should be injected slowly (1 to 2 mL per injection) into the surgical site using a ≥25 gauge needle and frequent aspirations should be done prior to and during administration; should not be filtered.
• It should not be administered epidurally, intrathecally, intravascularly, intra-articularly, or as a regional nerve block (except interscalene brachial plexus nerve block).
• Bupivacaine should not be allowed (liposomal) to come into contact with antiseptics (eg, povidone-iodine) in solution; when a topical antiseptic is applied, the application site should be allowed to dry prior to injection.
• Non-bupivacaine-based local anesthetics may cause bupivacaine (liposomal) to release immediately if administered together locally; therefore, after injection of lidocaine, administer bupivacaine no sooner than 20 minutes.
• Other local anesthetics or other formulations of bupivacaine should not be administered within 96 hours following bupivacaine (liposomal) administration; ma administer bupivacaine hydrochloride simultaneously in the same syringe or injected immediately before bupivacaine (liposomal) as long as the milligram ratio of bupivacaine hydrochloride to bupivacaine (liposomal) does not exceed 1:2.

Mechanism of action of Liposomal bupivacaine (Exparel):

• After the administration of liposomal buprevaine, the initiation and conduction nerve impulses are blocked by decreasing the neuronal membrane’s permeability for sodium ions.
• This causes inhibition of depolarization and conduction blockade.

Initial:

• Action is quick.

Time:

• 72 hours when administered locally. In the case of systemic, plasma levels may persist for up to 96 hours after local administration. 120 hours after interscalenebrachial plexus nerve blocking.

Absorption

• Systemic absorption can vary depending on the dosage, route and vascularity at the site of administration.

Protein binding:

• Highly protein-bound (95%)

Metabolism:

• Via conjugation reaction within the liver; pipecoloxylidine is the major metabolite (PPX; inactive).

Half-life elimination:

• 13 to 34 hours

Time to peak, plasma:

• Initial peak is within 1 hour while the second peak is within 12 to 36 hours

Excretion:

• Via Urine (~6% unchanged)

International Brand Names of Liposomal bupivacaine:

• Exparel

Liposomal bupivacaine Brand Names in Pakistan:

No Brands Available in Pakistan.