Liposomal bupivacaine is a specialized form of the local anesthetic medication bupivacaine. Local anesthetics are used to block pain signals in specific areas of the body during surgical or medical procedures. Liposomal bupivacaine is unique because it is delivered in a liposome-encapsulated form, which allows for extended release and prolonged pain relief.

Liposomes are tiny, spherical lipid vesicles that can encapsulate drugs like bupivacaine. When liposomal bupivacaine is administered, the liposomes slowly release the medication, providing a longer duration of pain relief compared to traditional, non-liposomal bupivacaine injections.

This extended-release property can be particularly beneficial for managing post-operative pain, as it reduces the need for frequent re-administration of the drug and minimizes the potential for side effects associated with high doses of local anesthetics. Liposomal bupivacaine is commonly used in various surgical procedures, including orthopedic surgeries, dental procedures, and some types of regional anesthesia.

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.

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Liposomal bupivacaine (Exparel) Dose in Adults:

Note: Bupivacaine (liposomal) and regular bupivacaine are not the same and can't be easily swapped. You can't convert the dose of one into the other. They work differently, so they're not interchangeable.

Liposomal bupivacaine (Exparel) Dose in postsurgical Analgesia:

Liposomal bupivacaine is used for pain relief after surgeries. When given as a local anesthesia through infiltration (directly into the surgical site), the dose depends on the surgery and the patient. There's a maximum dose limit of 266 mg (which is equivalent to 20 mL).

For specific surgeries:

• Bunionectomy (a surgery on the big toe):
  • 7 mL of undiluted liposomal bupivacaine is given around the bone cut (osteotomy).
  • Plus, 1 mL of the same undiluted drug is given just under the skin of the surgical area.
  • This gives a total of 106 mg, which is equal to 8 mL.
• Hemorrhoidectomy (a surgery to remove hemorrhoids):
  • 30 mL is given, but this is a diluted mix. To make this mix, 20 mL of liposomal bupivacaine is combined with 10 mL of a saline solution (NS).
  • This mixture is then divided into 6 parts, and each part (5 mL) is given around the muscle that controls the anus (anal sphincter).
  • The total dose is 266 mg or 20 mL.

This is a general guideline. The actual dose and how it's given may depend on the patient's needs and the doctor's judgment.

Liposomal bupivacaine (Exparel) Dose in Regional analgesia:

• Total shoulder arthroplasty or rotator cuff repair:
  • A single dose of 133 mg is used, which is equivalent to 10 mL.

This means that for surgeries like total shoulder replacements or rotator cuff repairs, a 10 mL dose of liposomal bupivacaine (amounting to 133 mg) is administered to the interscalene region of the brachial plexus to numb the shoulder and upper arm area.

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Use in Children:

Not indicated.

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Pregnancy Risk Category: C

• Studies on animals have shown that bupivacaine can cause harm during pregnancy.
• It can pass to the baby through the placenta.
• It's advised not to use bupivacaine when pregnant.
• Specifically, it shouldn't be used for a type of anesthesia near the cervix during childbirth because it can slow down the baby's heartbeat and may be fatal.

Use during breastfeeding:

• Bupivacaine can be found in breast milk.
• The company that makes it says that if you're breastfeeding and need this medicine, you should weigh the possible risks to your baby against the benefits of breastfeeding and the advantages of the treatment for you.

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Liposomal bupivacaine Dose in Kidney Disease:

• The company that makes bupivacaine doesn't give specific dose changes for people with kidney problems.
• But, having kidney issues might slow down how the body gets rid of bupivacaine, which could increase the risk of side effects.
• So, it should be used carefully in those with kidney concerns.

Liposomal bupivacaine Dose in Liver disease:

• The manufacturer doesn't specify dose changes for bupivacaine.
• If someone has serious health issues that affect how the body processes the drug, it could lead to more bupivacaine in the system, increasing the risk of side effects.
• So, it's important to use it with caution in such cases.

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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

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Contraindications to Liposomal bupivacaine (Exparel):

• An obstetrical paracervical block anesthesia is a medical procedure often used during childbirth. It involves injecting a local anesthetic (like bupivacaine or lidocaine) into the area around the cervix (the lower part of the uterus) to provide pain relief during labor. This type of anesthesia can help numb the cervix and surrounding tissues, making the process of childbirth more comfortable for the mother.

Warnings and precautions

CNS effects

• CNS effects refer to the impact on the central nervous system.
• Bupivacaine and other local anesthetics can sometimes cause either excitation (overactivity) or depression (underactivity) of the CNS.
• This can lead to severe outcomes like seizures, unconsciousness, or even stopping breathing.
• The risk of these effects can depend on how much of the drug is given, how it's given, and the overall health of the patient.
• It's crucial to watch for any changes in the patient's mental state or consciousness after each injection.
• Also, using local anesthetics like bupivacaine can sometimes lead to problems in the nerves, such as constant numbness, tingling, weakness, or even paralysis.
• Unfortunately, in some cases, these nerve effects might not go away.

CNS toxicity:

• CNS toxicity refers to harmful effects on the central nervous system due to certain substances, like local anesthetics.
• After giving a local anesthetic injection, it's crucial to keep a close watch on the patient.
• Signs that the CNS might be affected include feeling restless, anxious, speaking unclearly, feeling lightheaded, experiencing numbness or tingling around the mouth and lips, tasting something metallic, twitching, hearing ringing sounds, feeling dizzy, seeing blurred, shaking, feeling down, or feeling sleepy.
• These symptoms can be early signs that something is not right.
• If someone has sensory (feeling) or motor (movement) loss after the injection, it's usually temporary.
• This loss of sensation or movement can last up to 5 days but should then improve.

Cardiovascular toxicity:

• Cardiovascular toxicity refers to harmful effects on the heart and blood vessels.
• Using local anesthetics at high levels can lead to dangerous heart-related side effects.
• These might include a drop in heart function and blood pressure, disruptions in the heart's normal rhythm (like atrioventricular block and abnormal heartbeats), and even heart stoppage (cardiac arrest).
• These reactions can be life-threatening and require immediate medical attention.

Hypersensitivity reactions

• Hypersensitivity reactions are allergic reactions that can happen when using some drugs, including local anesthetics.
• In rare cases, after using the drug, some people might experience swelling that can affect the throat (angioneurotic edema, including laryngeal edema), feeling dizzy, a rise in body temperature, excessive sweating, nausea, fainting (syncope), a fast heartbeat (tachycardia), itching (pruritus), skin redness (erythema), sneezing, skin hives (urticaria), or vomiting.
• In some extreme cases, people can also experience severe reactions that resemble anaphylaxis, like significant drops in blood pressure (severe hypotension).
• It's also worth noting that if someone is allergic to one amide-type local anesthetic, they might also be allergic to others in the same group, as cross-sensitivity has been reported.

Infusion-related intra-articular chondrolysis

• Using local anesthetics directly inside a joint (intra-articular infusion) continuously after procedures like arthroscopy isn't an approved method.
• There have been instances where this has led to chondrolysis, which is the breaking down of cartilage, especially in the shoulder joint.
• In some of these cases, the damage was so severe that the patient needed surgery like joint replacement or another procedure called arthroplasty.

Methemoglobinemia:

• Methemoglobinemia is a condition where an abnormal form of hemoglobin is produced, reducing the blood's ability to carry oxygen.
• This condition has been reported with the use of local anesthetics.
• If methemoglobinemia is significant and causing clinical problems, immediate treatment is necessary, and the use of the anesthetic and other substances that can cause oxidation should be stopped.
• Symptoms can appear right away or even hours after exposure to the anesthetic.
• People with certain conditions like glucose-6-phosphate dehydrogenase deficiency, congenital or unexplained methemoglobinemia, heart or lung issues, exposure to substances that promote oxidation, or babies under six months old are more at risk.
• They should be closely monitored for signs of methemoglobinemia, such as bluish skin (cyanosis), headache, fast heartbeat, shortness of breath, feeling dizzy, and fatigue.

Respiratory arrest

• Local anesthetics, in rare cases, have been linked to sudden stopping of breathing, known as respiratory arrest.
• It's crucial to monitor patients closely when these drugs are administered to quickly address any breathing issues.

Seizures:

• Seizures or convulsions can sometimes happen due to the toxic effects of local anesthetics in the body.
• In some cases, these seizures can lead to the heart stopping, known as cardiac arrest.
• It's important to use these drugs with caution and monitor patients closely.

Cardiovascular disease

• People with heart problems should be careful when using bupivacaine.
• If they have weakened heart function, they might struggle with certain effects the drug can have, especially when it comes to changes in the heart's electrical conduction (like AV conduction).
• In simple terms, if someone already has heart issues, bupivacaine might make it harder for their heart to adjust to certain changes caused by the drug.

Hepatic impairment

• People with liver problems should be careful when using bupivacaine.
• If they have serious liver issues, they might be more at risk for harmful effects from the drug.
• This is because the liver plays a role in processing and getting rid of medications, and if it's not working well, the drug might stay in the system longer, increasing the risk of side effects.

Renal impairment

• People with kidney problems should use bupivacaine cautiously.
• If their kidneys aren't working well, they might have a higher risk of harmful effects from the drug.
• This is because kidneys help remove drugs from the body, and if they're impaired, the drug might not be cleared out as efficiently, leading to increased chances of side effects.

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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

Risk Factor C (Monitor therapy).
Hyaluronidase	Local anesthetics can have toxic or adverse effects that may be increased.
Methemoglobinemia associative Agents	Local anesthetics can have more harmful/toxic side effects. Methemoglobinemia risk may increase.
Neuromuscular-Blocking Agents	The neuromuscular-blocking effect of Neuromuscular-Blocking Agents may be enhanced by Local Anesthetics.
Technetium Tc 99m Tilmanocept	Technetium Tc99m Tilmanocept can be reduced by local anesthetics. Management: Avoid simultaneous co-injecting technetium Tc99m tilmanocept and local anesthetics. This interaction appears to not apply to other combinations of these agents.
Risk Factor D (Consider therapy modifications)
Bupivacaine	Liposomal Bupivacaine can have toxic or adverse effects. Management: Bupivacaine may be administered immediately prior to or in the same admixture syringe with liposomal bupivacaine. However, the ratio of the milligram dosage of bupivacaine and liposomal bupivacaine must not exceed 1:1.
Lidocaine (Systemic)	Bupivacaine (Liposomal), may have more toxic/adverse effects. Management: Avoid using topical lidocaine with Liposomal Buvacaine. After lidocaine administration, Liposomal buvacaine may be administered for up to 20 minutes.
Risk Factor X (Avoid Combination)
Local Anesthesia	Liposomal Bupivacaine can have toxic or adverse effects that may be increased. Management: Avoid administering Liposomal Bupinacaine with local anesthetics. You may administer Liposomal bupivacaine for up to 20 minutes after administration of lidocaine. However, the optimal time to separate doses of other local anesthetics such as Benzocaine or Benzydamine is not known.

Monitoring parameters:

Cardiovascular Signs

• Check the heart rate and blood pressure regularly.

Respiratory Signs

• Make sure breathing is normal and effective.

Consciousness

• Keep track of the patient's alertness and understanding.

CNS Toxicity Signs

• Look out for symptoms like restlessness, confusion, or seizures.

Pain Relief

• Monitor how well the pain is controlled and if relief is effective.

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How to administer Liposomal bupivacaine (Exparel)?

Dilution:

• Can be given in its original concentration (undiluted) or mixed with another solution (diluted).

Injection Technique:

• Inject slowly, giving 1 to 2 mL at a time.
• Use a needle that is 25 gauge or bigger.
• Frequently pull back on the syringe before and while injecting to make sure you're not in a blood vessel.
• Don't use a filter.

Where NOT to Inject:

• Avoid giving in the spine (epidurally or intrathecally).
• Don't inject into blood vessels, joints, or as a general nerve block. The only exception is the interscalene brachial plexus nerve block.

Avoiding Contamination:

• Don't let the medicine touch antiseptics like povidone iodine. If you use an antiseptic on the skin, wait until it dries before injecting.

Combining with Other Anesthetics:

• If using with other local anesthetics, like lidocaine, give bupivacaine at least 20 minutes after the lidocaine.
• Don't give other local anesthetics or different bupivacaine formulations within 96 hours after using bupivacaine (liposomal).
• If using with bupivacaine hydrochloride, they can be in the same syringe or given one after the other. Just make sure the amount (in milligrams) of bupivacaine hydrochloride is no more than half the amount of bupivacaine (liposomal).

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Mechanism of action of Liposomal bupivacaine (Exparel):

• Bupivacaine blocks the way nerves send and receive signals.
• It makes the outer layer of nerve cells less receptive to sodium ions.
• This stops the nerve cells from activating, which means they can't send pain signals.
• As a result, the area where bupivacaine is applied becomes numb.

Onset:

• Starts working quickly (Rapid onset as per Hu 2013).

Duration:

• Local Effect: The numbing effect can last up to 72 hours (Hu 2013).
• Systemic: Bupivacaine can be detected in the bloodstream for 96 hours after a local injection and 120 hours after an interscalene brachial plexus nerve block.

Absorption:

• How much gets into the system depends on the dose, how it's given, and blood flow to the site where it's administered.

Protein Binding:

• 95% of bupivacaine binds to proteins in the blood.

Metabolism:

• The liver breaks it down, mainly into an inactive substance called pipecoloxylidine (PPX).

Half-life:

• It takes 13 to 34 hours for half the drug to be eliminated from the system (Hu 2013).

Time to Peak, Plasma:

• It reaches its initial highest level in the blood within 1 hour, and then a second peak occurs between 12 to 36 hours (Hu 2013).

Excretion:

• It's mainly removed from the body in the urine, with around 6% leaving the body unchanged.

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International Brand Names of Liposomal bupivacaine:

• Exparel

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Liposomal bupivacaine Brand Names in Pakistan:

Not Available.